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Doi:10.1016/j.mito.2007.07.00

Available online at www.sciencedirect.com Mitochondrion 7 (2007) 359–366 G. Cannino, C.M. Di Liegro, A.M. Rinaldi * Dipartimento di Biologia Cellulare e dello Sviluppo ‘‘A.Monroy'', University of Palermo, Italy Received 3 April 2007; received in revised form 24 July 2007; accepted 24 July 2007 Available online 2 August 2007 The biogenesis of mitochondria depends on the coordinated expression of nuclear and mitochondrial genomes. Consequently, the control of mitochondrial biogenesis and function depends on extremely complex processes requiring a variety of well orchestrated reg-ulatory mechanisms. It is clear that the interplay of transcription factors and coactivators contributes to the expression of both nuclearand mitochondrial respiratory genes. In addition, the regulation of mitochondria biogenesis depends on proteins that, interacting withmessenger RNAs for mitochondrial proteins, influence their metabolism and expression. Moreover, a tight regulation of the import andfinal assembly of mitochondrial protein is essential to endow mitochondria with functional complexes. These studies represent the basisfor understanding the mechanisms involved in the nucleus–mitochondrion communication, a cross-talk essential for the cell.
Ó 2007 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
Keywords: Mitochondria; Transcriptional factors; Post-transcriptional regulation; RNA-binding proteins alterations (). Mitochondrial prolif- Eukaryotic cells contain a large number of mitochon- eration occurs in response to electrical stimulation of mus- dria, which are essential for cell metabolism. In fact, these cle, following training exercise (and during organelles perform pyruvate dehydrogenation, Kreb's thermogenesis adaptation in rodent brown fat cycle, and oxidative phosphorylation, the energy-generat- Proliferation of defective mitochondria ing processes coupling the oxidation of substrates to the takes place in certain mitochondrial myopathies, in which synthesis of nearly all cellular ATP. In addition, mitochon- affected muscles are characterized by the presence of rag- dria are involved in the synthesis of amino acids, nucleo- ged red fibres ). Presumably, this pro- liferation is a nuclear response to mitochondrial DNA proliferation, motility and programmed death (mtDNA) mutations leading to deficiencies in ATP produc- tion, but the mechanisms underlying these events are Mitochondria malfunctioning is related to aging poorly understood at the molecular level. Mitochondrial and to the onset of many diseases, including cancer proliferation and massive amplification of mtDNA take place during oogenesis in sea urchin. The resulting mito- ). The number, structure, and func- chondrial genomes are distributed to the embryo cells until tions of mitochondria differ in animal cells and tissues in very late developmental stages, when embryonic mtDNA relation to the energetic needs replication resumes ( and they can vary during development and differen- Interestingly, mitochondrial mass in Para- tiation, or in response to physiological or environmental centrotus lividus embryos is constant during development,while respiratory activity is enhanced at fertilization and increases from 16 blastomeres until gastrula Corresponding author. Tel.: +39 0916577441; fax: +39 0916577430.
E-mail address: (A.M. Rinaldi).
Experiments on enucleated sea urchin eggs 1567-7249/$ - see front matter Ó 2007 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
doi:10.1016/j.mito.2007.07.001 G. Cannino et al. / Mitochondrion 7 (2007) 359–366 demonstrated that a negative control is exerted by the 2. Transcriptional regulation nucleus over mitochondrial mtDNA activity: mitochon-drial DNA does not replicate, and it is not transcribed, The identification of transcription factors regulating the as long as the nucleus is present ( expression of nuclear genes encoding mitochondrial respi- Mitochondrial genome consists of a double- ratory components represents a good experimental tool stranded covalently closed circular DNA molecule of about for elucidating the mechanisms involved in the intergenom- 16.5 kb in vertebrates. Many mtDNA molecules are pack- ic cross-talk (). In general, it is aged within mitochondria into small clusters called nucle- thought that several regulatory circuits might exist in oids (), or chondriolites, that vary in response to different physiological stimuli, or that different size and number in response to physiological conditions regulatory pathways are activated for the expression of dif- ferent groups of genes. In other words, several factors reg- Nucleoid structure is stabilized by TFAM, ulating the transcription of many nuclear genes for or mtTFA, which binds to mtDNA and regulates its abun- mitochondrial proteins were isolated, but so far no com- dance (The maintenance of the integrity mon feature has been identified for the regulation of all of mitochondrial DNA is important for keeping proper cel- involved genes in a coordinated manner lular functions both under physiological and pathological The promoters of many genes conditions ). Mitochondria contains coding for OXPHOS proteins and other mitochondrial about 1500 different proteins, only half of which have been enzymes were characterized. It was demonstrated that they identified ). Metazoan mtDNA encodes do not exhibit canonical TATA and CAAT boxes, have 13 mRNAs for subunits of the oxidative phosphorylation heterogeneous initiation sites, and contain complex and complexes (OXPHOS) ( promoter-specific regulatory regions that can differ even ). Proteins of mitochon- among genes encoding subunits of the same complex ( drial origin are translated on mitochondrial ribosomes The expression of many proteins of bound to the matrix side of the inner membrane, and co- the OXPHOS complexes, like cytochrome c oxidase, the translationally inserted into the proper compartment ( terminal component of mitochondrial respiratory chain, is regulated at transcriptional level through specific mRNAs for mitochondrial proteins are transcribed in the nucleus-encoded factors nucleus () and translated by cytoplasmic ribo- ). NRF1 (nuclear respiratory factor 1), the first iso- somes. Proteins are eventually imported into mitochondria lated mammalian factor common to the expression of ) and distributed to different com- nuclear respiratory genes, functions as a positive regulator partments (inner and outer membrane, matrix and inter- of transcription ( membrane space) ). These The target genes of NRFs (NRF-1 and NRF-2) two pathways must converge at some point for those mul- encode subunits of the OXPHOS complexes or proteins timeric complexes assembling nuclear and mitochondrial involved in the expression, assembly, and function of the gene products. It is noteworthy that the machineries for complexes ). In mammals, it has been dem- both pathways are composed entirely by nuclear-coded onstrated that NRF-1 is able to bind the promoters of proteins. Recently, by genomic and proteomic approaches, genes encoding components of mtDNA transcription experiments were devoted to identify new pathways for the machinery (TFAM, TFB1M, TFB2M, and POLRMT) biogenesis of the inner and outer membranes, for the (whose mechanisms of action are being assembly and export of proteins from matrix to the inner established (More- membrane and for the addition of new components to over, NRF-1 seems to be related to the expression of mito- the existing pathways ().
chondrial and cytosolic enzymes of the heme biosynthetic One group of nuclear genes contributes with catalytic pathway, and to components of the protein import and and auxiliary proteins to the mitochondrial enzymatic assembly machinery, suggesting that it plays a role in activity. A second group includes all the factors that regu- late the expression of nuclear and mitochondrial OXPHOS NRF-2 regulates the transcription of mtTFA in human, genes ), while a third group encodes factors mouse, and rat (and mtTFA responsible for the import, assembly, and final localization is responsible for the transcription of the mitochondrial- of mitochondrial polypeptides ( encoded COX subunits I, II, and III, that are transcribed ). Thus, nuclear genome has a leading role in the bio- polycistronically synthesis of the respiratory chain ( Ongwijitwat and Wong-Riley demonstrated nevertheless, although rela- that, in neurons, NRF-2 is able to regulate all the tively few, mitochondrion-encoded proteins participate in nuclear-encoded COX subunits at the transcriptional level.
the formation of mitochondrial oxidative phosphorylation Thus, NRF-2 may play a critical role in regulating the syn- thesis of the cytochrome c oxidase subunits in response to Moreover, nuclear activity can be modulated by signals changes in neuronal energy demand sent by mitochondria ().
Human cytochrome c1 promoter seems G. Cannino et al. / Mitochondrion 7 (2007) 359–366 to be modulated by two transcription factors, E2F1 and urchin embryos, we found evidence that at least one com- E2F6, but they do not exert the same effects on other addi- plex of 40 kDa can be formed by a region of the 30-UTR tional promoters of OXPHOS genes, suggesting that the of the hsp56 messenger RNA and a binding protein which members of the E2F family are not general modulators is more abundant in the outer mitochondrial membrane of OXPHOS gene expression ).
The activity of transcription factors is increased by coreg- ulators, which usually exist as multiprotein complexes in the nucleus. This class of proteins can be highly regulated and represents the primary targets of hormonal control other hand, they were described factors involved in post- and signal transduction pathways transcriptional regulation of mitochondrial RNAs, such ). The PGC-1 (peroxisome proliferator-activated as the RBP38 protein, probably implicated in RNA stabil- receptor (PPAR) coactivator 1) family plays a critical role ization (). In Saccharomyces cerevisiae, in the control of tissue-specific biological processes and in it was demonstrated that the translation and assembly of the regulation of mitochondrial oxidative metabolism the subunits II and III of COX complex depends upon (The PGC-1 coactivators are highly versa- nucleus-encoded translation activators, which specifically tile, interacting with different transcription factors that recognize the 50-untranslated leader of the mRNAs directly regulate the expression of certain nuclear genes ). We demonstrated for mitochondrial products that, in developing rat brain, the amounts of COXIII pro- these include NRF-1 tein and mRNA are not linearly related, suggesting that and NRF-2, whose genes are themselves targets of PGC- COXIII expression could also be regulated at post-tran- 1a (PGC-1a and b stimulate the biogene- scriptional levels ). Recently, we sis of mitochondria with different metabolic characteristics, described two different factors able to bind COXIII thus, by modulating the relative activity of these two coac- mRNA, present in the mitochondrial extracts of adult rat tivators, cells may achieve fine-tuning of mitochondrial brain and testis, respectively. These tissue-specific factors function in response to specific metabolic needs could participate in COXIII mRNA translation and/or localization in mitochondrial inner membrane Taken together, these data suggest that transcriptional ). Mitochondrial extracts from rat brain also factors and nuclear coactivators orchestrate the programs contain a factor able to bind COXIV mRNA 30-UTR, of expression of both genomes, essential to cellular energet- whose binding ability decreases during brain differentia- ics, therefore they can be considered main players of the tion. The same mRNA is bound by proteins present in communication between nucleus and mitochondria.
post-mitochondrial extracts from heart, kidney, and testis.
These results suggest the existence of different tissue-spe- 3. Post-transcriptional regulation cific post-transcriptional regulatory factors, or the occur-rence of post-translational modifications of the same Increasing evidences demonstrate the importance of mRNA localization, stability, and translation regulation During liver development in the control of gene expression, in both developmental ), in brown adipose and differentiated cells; such regulation mostly relies upon tissue ) and in kidney cells ( the activity of RNA-binding proteins ( the regulation of the expression of the b-sub- unit of the mitochondrial H+-ATP synthase is also exerted lar activity of RNA-binding proteins is regulated by their at the level of mRNA translation. The translation of b- abundance, by the availability of specific regulatory mole- mRNA mostly depends on the 30UTR of the mRNA that, cules and/or by post-translational modification of their interacting with the translational machinery binding activity ) and resembling internal ribosome entry sites Mili and colleagues described human LRP130 protein, component of the PPR (pentatricopeptide behaves as a positive regulator. In fetal liver and in hepato- repeat motif) group of RNA-binding proteins, which is mas, Cuezva and colleagues found proteins that, binding to localized both in the nucleus, where it is associated with the 30UTR of the mRNA (30 FBPs), interfere with the post-splicing mRNP complexes, and in mitochondria, translation-enhancing activity of the 30UTR of the mRNA where it binds polyadenylated mRNAs. This suggests that LRP130 could participate in coordinating the expression of hence regulating mitochondrial biogenesis in hepatocytes nuclear and mitochondrial genomes ( It was also found that mouse AKAP121 (kinase A anchoring protein) expressed in HeLa cells carries MnSOD Since many data exist concerning the activity of RNA- mRNA in proximity of mitochondrial outer membrane, binding proteins in both multicellular and unicellular promoting its translation, thus facilitating the import into systems, it is possible to hypothesize that, despite the bio- mitochondria Interestingly, in sea logical differences between models, the regulation involving G. Cannino et al. / Mitochondrion 7 (2007) 359–366 protein–mRNA interactions might represent a general membranes, insertion of essential cofactors, assembly and mechanism of the regulation of nuclear–mitochondrial final maturation of the enzyme A novel gene product of the dihydrolipoamide suc- Reversible protein acetylation is emerging as a critical cinyltransferase gene, MIRTD (mitochondrial respiration post-translational modification involved in the regulation generator of truncated DLST), mediates the molecular of many biological processes. Although most of the pio- assembly of the cytochrome c oxidase complex (COX), so neering experiments focused on the role of histone acetyla- that MIRTD mRNA decrease could affect energy produc- tion in transcriptional control, recent findings have tion. The level of MIRTD mRNA is significantly low in the generalized the concept to many non-histone proteins brains of AD (Alzheimer's disease) patients, also confirm- Interestingly, it was demon- ing the idea that COX defect can cause the disease ( strated that mammalian mitochondria contain intrinsic NAD-dependent deacetylase activity. This deacetylase is In conclusion, different post-transcriptional and post- the nuclear-encoded SirT3, homologous to yeast Sir2 ( translational mechanisms operate in the regulation of mito- and it is located within mitochondrial chondrial biogenesis and activity. Future investigation matrix. SirT3 activity could lead to the constitutive deacet- efforts should be devoted to the understanding of the rela- ylation of one or several mitochondrial proteins tionships between the components of these regulation ). SirT3 activates mitochondrial functions and plays an important role in adaptive thermogenesis, stimu-lating CREB phosphorylation, which directly activates 4. Mitochondria to nucleus communication PGC-1a promoter ). Recently, it was foundthat, under normal cell growth conditions, SirT3 localizes Nuclear gene expression can be influenced by signals not only to mitochondria, but also to the nucleus, and it coming from mitochondria, a process called retrograde is transported from the nucleus to mitochondria upon cell stress ). SirT1, another mammalian homolog of yeast Sir2, was shown to modulate PGC-1a, so that the regulation of mitochondrial activity leading to enhanced transcriptional activity in an NAD+- depends on a bidirectional flow of information. In yeast, dependent way ) and, in addition, the retrograde signaling pathway functions as a homeo- inducing a metabolic gene transcription program of static or stress response mechanism, to adapt various mitochondrial fatty acid oxidation biosynthetic activities to the alterations of metabolic Mitochondrial activity is regulated also by modulating Sekito and collabora- the import and assembly of proteins and, during the last tors suggested a model for the control of signaling from years, several novel components of these pathways have mitochondria to nucleus, in which the cells with dysfunc- been identified. TIM23 complex and the presequence trans- tional mitochondria send one or more signals to nucleus locase-associated motor, the PAM complex, mediate the via Rtg2p: the dephosphorylation of a highly phosphor- multistep import of pre-proteins with cleavable N-terminal ylated form of Rtg3p leads to its transient dissociation signal sequences into the matrix or inner membrane of from Rtg1p and to the translocation of Rtg1p and Rtg3p mitochondria ), while the inner to the nucleus. Here they bind the GTCAC box sites of membrane contains several components that mediate the target genes and consequently activate transcription sorting and assembly of these proteins. Together, the trans- In skeletal mammalian myoblasts and in location and assembly complexes coordinate mitochondria human pulmonary carcinoma cells, mitochondrial retro- biogenesis Moreover, increasing evidences grade signaling seems to occur through cytosolic [Ca2+]i indicate that chaperones participate not only in protein folding, but also in assembling and maintaining mitochon- The alteration of mitochondrial membrane potential drial complexes ). A recently (DW) reduces mitochondrial Ca2+ uptake and, in turn, discovered sorting and assembly machinery (SAM com- it reduces ATP availability, causing reduction of calcium plex) is essential for integration and assembly of outer- efflux into storage organelles or outside the cells.
membrane proteins (). For example, Increased cytosolic Ca2+ concentration in turn activates the pathway of VDAC (voltage-dependent anion-selective calcineurin, and related factors such as Ca2+-dependent channel) biogenesis in human mitochondria involves the kinases, causing the activation of different nuclear tran- TOM complex, Sam50, and metaxins. The deletion of scription factors (Interest- Sam50, the central component of SAM, led to a defect in ingly, the absence of mitochondrial function blocks the assembly of VDAC ( myotube differentiation, probably through the specific Cytochrome c oxidase (COX) biogenesis includes a variety of steps from translation to the formation of the mature (). The retrograde signaling could complex. Each step involves a set of specific factors that be realized by the translocation of some mitochondrial assist translation of subunits, their translocation across proteins to the cytoplasm, and/or into the nucleus.
G. Cannino et al. / Mitochondrion 7 (2007) 359–366 According to such hypothesis, we recently found that, in 6. Concluding remarks developing rat brain, cytochrome c oxidase subunit III islocalized not only in mitochondria, but is also present in Mitochondrial function must rely on an orchestrated the cytosol (), where it could exert a cross-talk between nuclear and mitochondrial genes and, regulatory role.
although the genomes are physically distinct, they should Even if these data were obtained in different systems and be considered interdependent from the functional point the molecular mechanisms so far described are different, of view. In this review, we discuss the communication one can look at retrograde communication as a common between nucleus and mitochondria and the mechanisms necessary mechanism modulating nuclear–mitochondrial that could regulate this complex interplay. From the above-mentioned works, it appears clear that nucleus hasa dominant role in the regulation of mitochondrial activity.
5. Mitochondria and cancer Nuclear-coded transcriptional factors control the activityof mitochondrial genome, coordinating the expression of Genetic and/or epigenetic alterations of mitochondrial both nuclear and mitochondrial genes for mitochondrial functions cause a large variety of degenerative diseases, proteins. In addition, nucleus activity makes use of pro- aging, and cancer teins that regulate translation, stability, and localization An expanding number of autosomal diseases of the mRNAs, both of nuclear and mitochondrial origin, were associated with mitochondrial DNA depletion and modulating developmental and/or tissue-specific expres- multiple deletions. These disorders are due to defects of sion. RBPs' activity could represent a mechanism involved intergenomic communication, in fact mutations of nuclear in the nucleus to mitochondrion communication. Other genes for mitochondrial proteins possibly disrupt the nor- nucleus-encoded proteins participate in the control of the mal cross-talk that regulates the number of mtDNA copies import of mitochondrial proteins and ensure the correct and expression of mitochondrial genes, as suggested by assembly of OXPHOS complexes. The coordination between transcriptional and post-transcriptional regulation An association between mitochondrial dysfunction and mechanisms might be due to ‘‘compensation'' factors, cancer was made by and metabolic responsible for the regulation of respiratory enzymes syn- aberrations associated with mitochondrial bioenergetic thesis, according to the requirements of subunits assembly functions in cancer cells were observed in fully functioning complexes. Nonetheless, nuclear gene The relationship between mitochondrial expression can be influenced by signals coming from mito- disorders and mutations was documented for several doz- chondria, through retrograde communication, so that the ens of nuclear genes encoding proteins directly or indi- regulation of mitochondrial activity requires a bidirectional rectly involved in the biogenesis of the respiratory chain flow of information.
complexes Most human car-cinomas express reduced amounts of the catalytic subunit of H+-ATP synthase (In con-trast, the expression of nuclear encoded cytochrome c Ackerman, S.H., Tzagoloff, A., 2005. Function, structure and biogenesis oxidase subunits increases in human prostate carcinoma of mitochondrial ATP synthase. Prog. Nucleic Acid Res. Mol. Biol. 80, (Indeed, mutant mtDNA in tumor cells is more abundant than mutated nuclear mar- Allen, S., Balabanidou, V., Sideris, D.P., 2005. Erv1 mediates the mia40- dependent protein import pathway and provides a functional link to ker so that mtDNA mutations were the respiratory chain by shuttling electrons to cytochrome c. J. Mol.
used as clonal markers in hepatocellular carcinoma Biol. 353, 937–944.
(and breast cancer ( Amuthan, G., Biswas, G., Ananadatheerthavarada, H.K., Vijayasarathy, Interestingly, mitochondrial disfunction resulting C., Shephard, H.M., Avadhani, N.G., 2002. Mitochondrial stress- induced calcium signaling, phenotypic changes and invasive onbehavior in human lung carcinoma A549 cells. Oncogene 21, 7839– nucleus retrograde responses in human cells ( ). Kulawiec and colleagues, using Anderson, S., Bankier, A.T., Barrell, B.G., de-Bruijn, M.H.L., Coulson, a proteomic analysis, compared a cell line missing mito- A.R., Drouin, J., Eperon, I.C., Nierlich, D.P., Roe, B.A., Sanger, F., chondrial genome and a cybrid cell line in which mtDNA Schreier, H.P., Smith, A.J.H., Stader, R., Young, I.G., 1981. Sequence had been restored. They demonstrated changes in the and organization of the human mitochondrial genome. Nature 290,427–465.
expression of several proteins, and suggested that retro- Asin-Cayuela, J., Gustafsson, C.M., 2007. Mitochondrial transcription and grade responsive genes may potentially function as tumor its regulation in mammalian cells. Trends Biochem. Sci. 32, 111–117.
suppressor or oncogenes ). These Attardi, G., Schatz, G., 1988. Biogenesis of mitochondria. Annu. Rev.
studies show the correlation between functional defects Cell. Biol. 4, 289–333.
of mitochondria and tumorigenesis, and suggest that ret- Biswas, G., Adebanjo, O.A., Freedman, B.D., Anandatheerthavarada, H.K., Vijayasarathy, C., Zaidi, M., Kotlikoff, M., Avadhani, N.G., rograde signaling may be an important factor in restoring 1999. Retrograde Ca2F signaling in C2C12 skeletal myocytes in response to mitochondrial genetic and metabolic stress: a novel mode of inter-organelle crosstalk. EMBO J. 18, 522–533.
G. Cannino et al. / Mitochondrion 7 (2007) 359–366 Brandon, M., Baldi, P., Wallace, D.C., 2006. Mitochondrial mutations in Gerhart-Hines, Z., Rodgers, J.T., Bare, O., Lerin, C., Kim, S.H., cancer. Oncogene 25, 4647–4662.
Mostoslavsky, R., Alt, F.W., Wu, Z., Puigserver, P., 2007. Metabolic Butow, R.A., Avadhani, N.G., 2004. Mitochondrial signaling: the control of muscle mitochondrial function and fatty acid oxidation retrograde response. Mol. Cell 14, 1–15.
through SIRT1/PGC-1alpha. EMBO J. 26, 1913–1923.
Calvo, S., Jain, M., Xie, X., Sheth, S.A., Chang, B., Goldberger, O.A., Ginsberg, M.D., Feliciello, A., Jones, J.K., Avvedimento, E.V., Gottes- Spinazzola, A., Zeviani, M., Carr, S.A., Mootha, V.K., 2006.
man, M.E., 2003. PKA-dependent binding of mRNA to the mito- Systematic identification of human mitochondrial disease genes chondrial AKAP121 protein. J. Mol. Biol. 327, 885–897.
through integrative genomics. Nat. Genet. 38, 576–582.
Glick, B., Schatz, G., 1991. Import of proteins into mitochondria. Annu.
Cam, H., Balciunaite, E., Blias, A., Spektor, A., Scarpulla, R.C., Young, Rev. Genet. 25, 21–44.
R., Kluger, Y., Dynlacht, B.D., 2004. A common set of gene Goffart, S., Wiesner, R.J., 2003. Regulation and co-ordination of nuclear regulatory networks links metabolism and growth inhibition. Mol.
gene expression during mitochondrial biogenesis. Exp. Physiol. 88, 33– Cell 16, 399–411.
Cannino, G., Di Liegro, C.M., Di Liegro, I., Rinaldi, A.M., 2004.
Herrmann, P.C., Gillespie, J.W., Charboneau, L., Bichsel, V.E., Paweletz, Analysis of cytochrome c oxidase subunits III and IV expression in C.P., Calvert, V.S., Kohn, E.C., Emmert-Buck, M.R., Liotta, L.A., developing rat brain. Neuroscience 128, 91–98.
Petricoin, E.F., 2003. Mitochondrial proteome: altered cytochrome c Cannino, G., Di Liegro, C.M., Luparello, C., Rinaldi, A.M., 2006.
oxidase subunit levels in prostate cancer. Proteomics 3, 1801–1810.
Mitochondrial protein expression in rat and in human cells. Caryo- Hirano, M., Vu, T.H., 2000. Defects of intergenomic communication: logia 59, 375–378.
where do we stand? Brain Pathol. 10, 451–461.
Capaldi, R.A., 1990. Structure and assembly of cytochrome c oxidase.
Hood, D.A., 2001. Contractile activity-induced mitochondrial biogenesis Arch. Biochem. Biophys. 280, 252–262.
in skeletal muscle. J. Appl. Physiol. 90, 1137–1157.
Caruso, F., Villa, R., Rossi, M., Pettinari, C., Paduano, F., Pennati, M., Izquierdo, J.M., Cuezva, J.M., 1997. Control of the translational efficiency Daidone, M.G., Zaffaroni, N., 2007. Mitochondria are primary targets of beta-F1-ATPase mRNA depends on the regulation of a protein that in apoptosis induced by the mixed phosphine gold species chlorotri- binds the 30 untranslated region of the mRNA. Mol. Cell. Biol. 17, phenylphosphine-1,3 bis(diphenylphosphino)propanegold(I) in mela- noma cell lines. Biochem. Pharmacol. 73, 773–781.
Izquierdo, J.M., Cuezva, J.M., 2000. Internal-ribosome-entry-site func- Costanzo, M.C., Seaver, E.C., Fox, T.D., 1986. At least two nuclear gene tional activity of the 30-untranslated region of the mRNA for the beta products are specifically required for translation of a single yeast subunit of mitochondrial H+ATP synthase. Biochem. J. 346, 849–855.
mitochondrial mRNA. EMBO J. 5, 3637–3641.
Izquierdo, J.M., Ricart, J., Ostronoff, L.K., Egea, G., Cuezva, J.M., 1995.
Cuezva, J.M., Ostronoff, L.K., Ricart, J., Lopez de Heredia, M., Di Changing patterns of transcriptional and post-transcriptional control Liegro, C.M., Izquierdo, J.M., 1997. Mitochondrial biogenesis in the of h-F1-ATPase gene expression during mitochondrial biogenesis in liver during development and oncogenesis. J. Bioenerg. Biomembr. 29, liver. J. Biol. Chem. 270, 10342–10350.
Jacobs, H.T., Lehtinen, S.K., Spelbrink, J.N., 2000. No sex please, we're de Heredia, M.L., Izquierdo, J.M., Cuezva, J.M., 2000. A conserved mitochondria: a hypothesis on the somatic unit of inheritance of mechanism for controlling the translation of beta-F1-ATPase mRNA mammalian mtDNA. Bioessays 22, 564–572.
between the fetal liver and cancer cells. J. Biol. Chem. 275, 7430–7437.
Kang, D., Kim, S.H., Hamasaki, N., 2007. Mitochondrial transcription Derrigo, M., Cestelli, A., Savettieri, G., Di Liegro, I., 2000. RNA–protein factor A (TFAM): roles in maintenance of mtDNA and cellular interactions in the control of stability and localization of messenger functions. Mitochondrion 7, 39–44.
RNA. Int. J. Mol. Med. 5, 111–123.
Kanki, T., Nakayama, H., Sasaki, N., Takio, K., Alam, T.I., Hamasaki, Di Liegro, C.M., Rinaldi, A.M., 2007. Hsp56 mRNA in Paracentrotus N., Kang, D., 2004. Mitochondrial nucleoid and transcription factor lividus embryos binds to a mitochondrial protein. Cell Biol. Int. [Epub A. Ann. N. Y. Acad. Sci. 1011, 61–68.
ahead of print].
Keene, J.D., Lager, P.J., 2005. Post-transcriptional operons and regulons Di Liegro, C.M., Bellafiore, M., Izquierdo, J.M., Rantanen, A., Cuezva, co-ordinating gene expression. Chromosome Res 13, 327–337.
J.M., 2000. 30-untranslated regions of oxidative phosphorylation Kelly, D.P., Scarpulla, R., 2004. Transcriptional regulatory circuits mRNAs function in vivo as enhancers of translation. Biochem. J.
controlling mitochondrial biogenesis and function. Genes Dev. 18, 352, 109–115.
Dreyfuss, G., Kim, V.N., Kataoka, N., 2002. Messenger-RNA-binding Khalimonchuk, O., Ro¨del, G., 2005. Biogenesis of cytochrome c oxidase.
proteins and the messages they carry. Nat. Rev. Mol. Cell. Biol. 31, Mitochondrion 5, 363–388.
Klingenspor, M., Ivemeyer, M., Wiesinger, H., Haas, K., Heldmaier, G., Enriquez, J.A., Fernandez-Silva, P., Garrido-Perez, N., Lopez-Perez, Wiesner, R.J., 1996. Biogenesis of thermogenic mitochondria in brown M.J., Perez-Martos, A., Montoya, J., 1999. Direct regulation of adipose tissue of Djungarian hamsters during cold adaptation.
mitochondrial RNA syntesis by thyroid homone. Mol. Cell Biol. 19, Biochem. J. 316, 607–613.
Koehler, C.M., 2004. New developments in mitochondrial assembly.
Feige, J.N., Auwerx, J., 2007. Transcriptional coregulators in the control Annu. Rev. Biochem. 20, 309–335.
of energy homeostasis. Trends Cell Biol. 17, 292–301.
Kozjak-Pavlovic, V., Ross, K., Benlasfer, N., Kimmig, S., Karlas, A., Fernandez-Silva, P., Enriquez, J.A., Montoya, J., 2003. Replication and Rudel, T., 2007. Conserved roles of Sam50 and metaxins in VDAC transcription of mammalian mitochondrial DNA. Exp. Physiol. 88, biogenesis. EMBO Rep. 8, 576–582.
Kulawiec, M., Arnouk, H., Desouki, M.M., Kazim, L., Still, I., Singh, Fisher, R.P., Clayton, D.A., 1988. Purification and characterization of human K.K., 2006. Proteomic analysis of mitochondria-to-nucleus retrograde mitochondrial transcription factor 1. Mol. Cell. Biol. 8, 3496–3509.
response in human cancer. Cancer Biol. Ther. 5, 967–975.
Fliss, M.S., Usadel, H., Caballero, O.L., Wu, L., Buta, M.R., Eleff, S.M., Larsson, N.G., Wang, J., Wilhelmsson, H., Oldfors, A., Rustin, P., Jen, J., Sidransky, D., 2000. Facile detection of mitochondrial DNA Lewandoski, M., Barsh, G.S., Clayton, D.A., 1998. Mitochondrial mutations in tumors and bodily fluids. Science 287, 2017–2019.
transcription factor A is necessary for mtDNA maintenance and Garcia-Rodriguez, L.J., Gay, A.C., Pon, L.A., 2007. Puf3p, a Pumilio embryogenesis in mice. Nat. Genet. 18, 231–236.
family RNA binding protein, localizes to mitochondria and regulates Legros, F., Malka, F., Frachon, P., Lombe s, A., Rojo, M., 2004.
mitochondrial biogenesis and motility in budding yeast. J. Cell. Biol.
Organization and dynamics of human mitochondrial DNA. J. Cell Sci.
176, 197–207.
117, 2653–2662.
Garesse, R., Vallejo, C.G., 2001. Animal mitochondrial biogenesis and Lenka, N., Vijayasarathy, C., Mullick, J., Avadhani, N.G., 1998.
function: a regulatory cross-talk between two genomes. Gene 263, 1–16.
Structural organization and transcription regulation of nuclear genes G. Cannino et al. / Mitochondrion 7 (2007) 359–366 encoding the mammalian cytochrome c oxidase complex. Prog.
Parikh, V.S., Morgan, M.M., Scott, R., Clements, L.S., Butow, R.A., Nucleic Acid Res. Mol. Biol. 61, 309–344.
1987. The mitochondrial genotype can influence nuclear gene expres- Liao, X., Butow, R.A., 1993. RTG1 and RTG2: two yeast genes required sion in yeast. Science 235, 576–580.
for a novel path of communication from mitochondria to the nucleus.
Parrella, P., Xiao, Y., Fliss, M., Sanchez-Cespedes, M., Mazzarelli, P., Cell 72, 61–71.
Rinaldi, M., Nicol, T., Gabrielson, E., Cuomo, C., Cohen, D., Pandit, Liao, X., Small, W.C., Srere, P.A., Butow, R.A., 1991. Intramitochondrial S., Spencer, M., Rabitti, C., Fazio, V.M., Sidransky, D., 2001.
functions regulate nonmitochondrial citrate synthase (CIT2) expres- Detection of mitochondrial DNA mutations in primary breast cancer sion in Saccharomyces cerevisiae. Mol. Cell. Biol. 11, 38–46.
and fine-needle aspirates. Cancer Res. 61, 7623–7626.
Lin, J., Handschin, C., Spiegelman, B.M., 2005. Metabolic control Pfanner, N., Wiedemann, N., Meisinger, C., Lithgow, T., 2004. Assem- through the PGC-1 family of transcription coactivators. Cell Metab.
bling the mitochondrial outer membrane. Nat. Struct. Mol. Biol. 11, 1, 361–370.
Liu, Z., Butow, R.A., 2006. Mitochondrial retrograde signalling. Annu.
Pollak, J.K., Sutton, R., 1980. The differentiation of animal mitochondria Rev. Genet. 40, 159–185.
during development. Trends Biol. Chem. 5, 23–27.
Luciakova, K., Barath, P., Li, R., Zaid, A., Nelson, B.D., 2000. Activity of Poyton, R.O., McEwen, J.E., 1996. Crosstalk between nuclear and the human cytochrome c1 promoter is modulated by E2F. Biochem. J.
mitochondrial genomes. Annu. Rev. Biochem. 65, 563–607.
351, 251–256.
Puigserver, P., Spiegelman, B.M., 2003. Peroxisome proliferator-activated Luis, A.M., Izquierdo, J.M., Ostronoff, L.K., Salinas, M., Santaren, J.F., receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional Cuezva, J.M., 1993. Translational regulation of mitochondrial differ- coactivator and metabolic regulator. Endocr. Rev. 24, 78–90.
entiation in neonatal rat liver. J. Biol. Chem. 268, 1868–1875.
Raimondi, L., Cannino, G., D'Asaro, M., Sala, A., Savettieri, G., Di Malka, F., Lombe s, A., Rojo, M., 2006. Organization, dynamics and liegro, I., 2002. Regulation of RNA metabolism in the Nervous transmission of mitochondrial DNA: focus on vertebrate nucleoids.
System. Recent Res. Dev. Neurochem. 5, 39–48.
Biochim. Biophys. Acta 1763, 463–472.
Rinaldi, A.M., Salcher-Cillari, I., 1989. Studies of the mechanisms of Matsumoto, L., Kasamatsu, H., Piko´, L., Vinograd, J., 1974. Mitochon- nuclear control over the synthesis of mitochondrial DNA in sea urchin drial DNA replication in sea urchin oocytes. J. Cell Biol. 63, 46–159.
eggs. Cell Biol. Int. Rep. 13, 181–187.
McKenzie, M., Liolitsa, D., Hanna, M.G., 2004. Mitochondrial disease: Rinaldi, A.M., De Leo, G., Arzone, A., Salcher, I., Storace, A., Mutolo, mutations and mechanisms. Neurochemical Research 29, 589–600.
V., 1979a. Biochemical and electron microscopic evidence that cell Meisinger, C., Pfannschmidt, S., Rissler, M., Milenkovic, D., Becker, T., nucleus negatively controls mitochondrial genomic activity in early sea Stojanovski, D., Youngman, M.J., Jensen, R.E., Chacinska, A., urchin development. Proc. Natl. Acad. Sci. USA 76, 1916–1920.
Guiard, B., Pfanner, N., Wiedemann, N., 2007. The morphology Rinaldi, A.M., Salcher-Cillari, I., Mutolo, V., 1979b. Mitochondrial proteins Mdm12/Mmm1 function in the major beta-barrel assembly division in non nucleated sea urchin eggs. Cell Biol. Int. Rep. 3, 179–182.
pathway of mitochondria. EMBO J. 26, 2229–2239.
Rochard, P., Rodier, A., Casas, F., Cassar-Malek, I., Marchal-Victorion, Mendez, R., Hake, L.E., Andresson, T., Littlepage, L.E., Ruderman, J.V., S., Daury, L., Wrutniak, C., Cabello, G., 2000. Mitochondrial activity Richter, J.D., 2000. Phosphorylation of CPE binding factor by Eg2 is involved in the regulation of myoblast differentiation through regulates translation of c-mos mRNA. Nature 404, 302–307.
myogenin expression and activity of myogenic factors. J. Biol. Chem.
Mili, S., Pinol-Roma, S., 2003. LRP130, a pentatricopeptide motif protein 275, 2733–2744.
with a noncanonical RNA-binding domain, is bound in vivo to Rodgers, J.T., Lerin, C., Haas, W., Gygi, S.P., Spiegelman, B.M., mitochondrial and nuclear RNAs. Mol. Cell. Biol. 23, 4972–4982.
Puigserver, P., 2005. Nutrient control of glucose homeostasis through Modica-Napolitano, J.S., Kulawiec, M., Singh, K.K., 2007. Mitochondria a complex of PGC-1alpha and SIRT1. Nature 434, 113–118.
and human cancer. Curr. Mol. Med. 7, 121–131.
Ro¨tig, A., Munnich, A., 2003. Genetic features of mitochondrial respi- Moraes, C.T., 2001. What regulates mitochondrial DNA copy number in ratory chain disorders. J, Am. Soc. Nephrol. 14, 2995–3007.
animal cells? Trends Genet. 17, 199–205.
Sachs, A.B., Sarnow, P., Hentze, M.W., 1997. Starting at the beginning, Moraes, C.T., Ricci, E., Bonilla, E., DiMauro, S., Schon, E.A., 1992. The middle, and end: translation initiation in eukaryotes. Cell 89, 831–838.
mitochondrial tRNALeu(UUR) mutation in mitochondrial encephal- Sanchirico, M.E., Fox, T.D., Mason, T.L., 1998. Accumulation of omyopathy, lactic acidosis, and strokelike episodes (MELAS): genetic, mitochondrially synthesized Saccharomyces cerevisiae Cox2p and biochemical, and morphological correlations in skeletal muscle. Am. J.
Cox3p depends on targeting information in untranslated portions of Hum. Genet. 50, 934–949.
their mRNAs. EMBO J. 17, 5796–5804.
Morici, G., Agnello, M., Spagnolo, F., Roccheri, M.C., Di Liegro C.M., Santamarı´a, G., Martı´nez-Diez, M., Fabregat, I., Cuezva, J.M., 2006.
Rinaldi A.M., 2007. Confocal microscopy study of the distribution, Efficient execution of cell death in non-glycolytic cells requires the content and activity of mitochondria during Paracentrotus lividus generation of ROS controlled by the activity of mitochondrial H+- development. J. Microsc., in press.
ATP synthase. Carcinogenesis 27, 925–935.
Nagata, T., 2006. Electron microscopic radioautographic study on protein Saraste, M., 1999. Oxidative phosphorylation at the fin de siecle. Science synthesis in hepatocyte mitochondria of aging mice. Scientific World 283, 1488–1493.
Journal 15, 1583–1598.
Sbicego, S., Alfonzo, J.D., Estevez, A.M., Rubio, M.A., Kang, X., Turck, Neupert, W., 1997. Protein import into mitochondria. Annu. Rev.
C.W., Peris, M., Simpson, L., 2003. RBP38, a novel RNA-binding Biochem. 66, 863–917.
protein from trypanosomatid mitochondria, modulates RNA stability.
Nomoto, S., Sanchez-Cespedes, M., Sidransky, D., 2002. Identification of Eukaryotic cell. 2, 560–568.
mtDNA mutations in human cancer. Methods Mol. Biol. 197, 107– Scarpulla, R.C., 2002a. Transcriptional activators and co-activators in the nuclear control of mitochondrial function in mammalian cells. Gene Nosek, J., Tomaska, L., 2003. Mitochondrial genome diversity: evolution 286, 81–89.
of the molecular architecture and replication strategy. Curr. Genet. 44, Scarpulla, R.C., 2002b. Nuclear activators and co-activators in mamma- lian mitochondrial biogenesis. Biochim. Biophys. Acta 1576, 1–14.
Ohta, S., Ohsawa, I., 2006. Dysfunction of mitochondria and oxidative Scarpulla, R.C., 2006. Nuclear control of respiratory gene expression in stress in the pathogenesis of Alzheimer's disease: on defects in the mammalian cells. J. Cell. Biochem. 97, 673–683.
cytochrome c oxidase complex and aldehyde detoxification. J. Alzhei- Schatz, G., 1995. Mitochondria: beyond oxidative phosphorylation.
mers Dis. 9, 155–166.
Biochim. Biophys. Acta 1271, 123–126.
Ongwijitwat, S., Wong-Riley, M.T.T., 2005. Is nuclear respiratory factor 2 Scher, M.B., Vaquero, A., Reinberg, D., 2007. SirT3 is a nuclear a master transcriptional coordinator for all ten nuclear-encoded NAD+dependent histone deacetylase that translocates to the mito- cytochrome c oxidase subunits in neurons? Gene 360, 65–77.
chondria upon cellular stress. Genes Dev. 21, 920–928.
G. Cannino et al. / Mitochondrion 7 (2007) 359–366 Schwer, B., North, B.J., Frye, R.A., Ott, M., Verdin, E., 2002. The human Tanner, K.G., Landry, J., Sternglanz, R., Denu, J.M., 2000. Silent silent information regulator (Sir)2 homologue hSIRT3 is a mitochon- information regulator 2 family of NAD- dependent histone/protein drial nicotinamide adenine dinucleotide-dependent deacetylase. J. Cell deacetylases generates a unique product, 1-O-acetyl-ADP-ribose. Proc.
Biol. 158, 647–657.
Natl. Acad. Sci. 97, 14178–14182.
Sekito, T., Thornton, J., Butow, R.A., 2000. Mitochondria-to-Nuclear Tvrdik, P., Kuzela, S., Houstek, J., 1992. Low translational efficiency of Signaling Is Regulated by the Subcellular Localization of the Tran- the F1-ATPase beta-subunit mRNA largely accounts for the decreased scription Factors Rtg1p and Rtg3p. Mol. Biol. Cell 11, 2103–2115.
ATPase content in brown adipose tissue mitochondria. FEBS Lett.
Shi, T., Wang, F., Stieren, E., Tong, Q., 2005. SIRT3, a mitochondrial 313, 23–26.
sirtuin deacetylase, regulates mitochondrial function and thermogen- Valcarce, C., Navarrete, R.M., Encabo, P., Loeches, E., Satru´stegui, J., esis in brown adipocytes. J. Biol. Chem. 280, 13560–13567.
Cuezva, J.M., 1988. Postnatal development of rat liver mitochondrial Singh, K.K., 2006. Mitochondria damage checkpoint, aging, and cancer.
functions. The roles of protein synthesis and of adenine nucleotides. J.
Ann. N Y Acad. Sci. 1067, 182–190.
Biol. Chem. 263, 7767–7775.
Small, W.C., Brodeur, R.D., Sandor, A., Fedorova, N., Li, G., Butow, van der Laan, M., Rissler, M., Rehling, P., 2006. Mitochondrial R.A., Srere, P.A., 1995. Enzymatic and metabolic studies on preprotein translocases as dynamic molecular machines. FEMS Yeast retrograde regulation mutants in yeast. Biochemistry 16, 5569–5576.
Res. 6, 849–861.
Spiegelman, B.M., Heinrich, R., 2004. Biological control through regu- Wallace, D.C., 1999. Mitochondrial diseases in man and mouse. Science lated transcriptional coactivators. Cell 119, 157–167.
283, 1482–1488.
Sterner, D.E., Berger, S.L., 2000. Acetylation of histones and transcription Warburg, O., 1930. Metabolism of tumors. Arnold Constable, London.
related factors. Microbiol. Mol. Biol. Rev. 64, 435–459.
Wu, Z., Puigserver, P., Andersson, U., Zhang, C., Adelmant, G., Szabadkai, G., Rizzuto, R., 2007. Chaperones as parts of organelle Mootha, V., Troy, A., Cinti, S., Lowell, B., Scarpulla, R.C., networks. Adv. Exp. Med. Biol. 594, 64–77.
Spiegelman, B.M., 1999. Mechanisms controlling mitochondrial Taanman, J.W., 1999. The mitochondrial genome: structure, transcrip- biogenesis and respiration through the thermogenic coactivator tion, translation and replication. Biochim. Biophys. Acta Bio-Ener- PGC-1. Cell 98, 115–124.
getics. 1410, 103–123.
Yaffe, M.P., 1999. Dynamic mitochondria. Nat. Cell Biol. 1, 149–150.

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Impregnated central venous catheters for prevention of bloodstream infection in children (the catch trial): a randomised controlled trial

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