Abstract
Regulation of the expression of the nuclear-encoded beta-subunit of H(+)-ATP synthase (beta-F1-ATPase) gene of oxidative phosphorylation during differentiation of liver mitochondria is mainly exerted at two post-transcriptional levels affecting both the half-life [Izquierdo, Ricart, Ostronoff, Egea and Cuezva (1995) J. Biol. Chem. 270, 10342-10350] and translational efficiency [Luis, Izquierdo, Ostronoff, Salinas, Santarén and Cuezva (1993) J. Biol. Chem. 268, 1868-1875] of the transcript. Herein, we have studied the expression of the mitochondrial (mt) genome during differentiation of rat liver mitochondria in an effort to elucidate the mechanisms of nucleo-mitochondrial cross-talk during biogenesis of the organelle. Estimation of the relative cellular representation of met-DNA in liver reveals a negligible increase in mt-DNA copy number during organelle differentiation. Concurrently, the lack of changes in transcription rates of the mt-DNA "in organello', as well as in steady-state levels of the mt-transcripts, suggests that organelle differentiation is not controlled by an increase in transcription of the mt-genome. However, translation rates in isolated mitochondria revealed a transient 2-fold increase immediately after birth. Interestingly, the transient activation of mitochondrial translation at this stage of liver development is dependent on the synthesis of proteins in cytoplasmic polyribosomes. These findings support the hypothesis that the expression of nuclear and mitochondrial genes during biogenesis of mammalian mitochondria is developmentally regulated by a post-transcriptional mechanism that involves concerted translational control of both genomes.
Full Text
The Full Text of this article is available as a PDF (513.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Attardi G., Chomyn A., King M. P., Kruse B., Polosa P. L., Murdter N. N. Regulation of mitochondrial gene expression in mammalian cells. Biochem Soc Trans. 1990 Aug;18(4):509–513. doi: 10.1042/bst0180509. [DOI] [PubMed] [Google Scholar]
- Attardi G., Montoya J. Analysis of human mitochondrial RNA. Methods Enzymol. 1983;97:435–469. doi: 10.1016/0076-6879(83)97154-9. [DOI] [PubMed] [Google Scholar]
- Attardi G., Schatz G. Biogenesis of mitochondria. Annu Rev Cell Biol. 1988;4:289–333. doi: 10.1146/annurev.cb.04.110188.001445. [DOI] [PubMed] [Google Scholar]
- Brass E. P. Translation rates of isolated liver mitochondria under conditions of hepatic mitochondrial proliferation. Biochem J. 1992 Nov 15;288(Pt 1):175–180. doi: 10.1042/bj2880175. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cantatore P., Flagella Z., Fracasso F., Lezza A. M., Gadaleta M. N., de Montalvo A. Synthesis and turnover rates of four rat liver mitochondrial RNA species. FEBS Lett. 1987 Mar 9;213(1):144–148. doi: 10.1016/0014-5793(87)81480-1. [DOI] [PubMed] [Google Scholar]
- Cantatore P., Polosa P. L., Fracasso F., Flagella Z., Gadaleta M. N. Quantitation of mitochondrial RNA species during rat liver development: the concentration of cytochrome oxidase subunit I (CoI) mRNA increases at birth. Cell Differ. 1986 Sep;19(2):125–132. doi: 10.1016/0045-6039(86)90069-2. [DOI] [PubMed] [Google Scholar]
- Chamberlain J. P. Fluorographic detection of radioactivity in polyacrylamide gels with the water-soluble fluor, sodium salicylate. Anal Biochem. 1979 Sep 15;98(1):132–135. doi: 10.1016/0003-2697(79)90716-4. [DOI] [PubMed] [Google Scholar]
- Chang D. D., Clayton D. A. A mammalian mitochondrial RNA processing activity contains nucleus-encoded RNA. Science. 1987 Mar 6;235(4793):1178–1184. doi: 10.1126/science.2434997. [DOI] [PubMed] [Google Scholar]
- Christianson T. W., Clayton D. A. A tridecamer DNA sequence supports human mitochondrial RNA 3'-end formation in vitro. Mol Cell Biol. 1988 Oct;8(10):4502–4509. doi: 10.1128/mcb.8.10.4502. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clayton D. A. Nuclear gadgets in mitochondrial DNA replication and transcription. Trends Biochem Sci. 1991 Mar;16(3):107–111. doi: 10.1016/0968-0004(91)90043-u. [DOI] [PubMed] [Google Scholar]
- Clayton D. A. Replication and transcription of vertebrate mitochondrial DNA. Annu Rev Cell Biol. 1991;7:453–478. doi: 10.1146/annurev.cb.07.110191.002321. [DOI] [PubMed] [Google Scholar]
- England J. M., Costantino P., Attardi G. Mitochondrial RNA and protein synthesis in enucleated African green monkey cells. J Mol Biol. 1978 Mar 5;119(3):455–462. doi: 10.1016/0022-2836(78)90226-7. [DOI] [PubMed] [Google Scholar]
- Enriquez J. A., López-Pérez M. J., Montoya J. Saturation of the processing of newly synthesized rRNA in isolated brain mitochondria. FEBS Lett. 1991 Mar 11;280(1):32–36. doi: 10.1016/0014-5793(91)80197-b. [DOI] [PubMed] [Google Scholar]
- Enríquez J. A., Pérez-Martos A., Fernández-Silva P., López-Pérez M. J., Montoya J. Specific increase of a mitochondrial RNA transcript in chronic ethanol-fed rats. FEBS Lett. 1992 Jun 15;304(2-3):285–288. doi: 10.1016/0014-5793(92)80639-x. [DOI] [PubMed] [Google Scholar]
- Fernández-Silva P., Enriquez J. A., Montoya J. A simple procedure for recovering the denaturing effect of methylmercury in agarose gel electrophoresis. Biotechniques. 1992 Apr;12(4):480–482. [PubMed] [Google Scholar]
- Fisher R. P., Clayton D. A. Purification and characterization of human mitochondrial transcription factor 1. Mol Cell Biol. 1988 Aug;8(8):3496–3509. doi: 10.1128/mcb.8.8.3496. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gadaleta M. N., Minervini G. R., Renis M., De Giorgi C., Giovine A. Mitochondrial DNA, RNA and protein synthesis in normal and hypothyroid developing rat liver. Cell Differ. 1986 Jul;19(1):43–49. doi: 10.1016/0045-6039(86)90024-2. [DOI] [PubMed] [Google Scholar]
- Gadaleta M. N., Petruzzella V., Renis M., Fracasso F., Cantatore P. Reduced transcription of mitochondrial DNA in the senescent rat. Tissue dependence and effect of L-carnitine. Eur J Biochem. 1990 Feb 14;187(3):501–506. doi: 10.1111/j.1432-1033.1990.tb15331.x. [DOI] [PubMed] [Google Scholar]
- Garboczi D. N., Fox A. H., Gerring S. L., Pedersen P. L. Beta subunit of rat liver mitochondrial ATP synthase: cDNA cloning, amino acid sequence, expression in Escherichia coli, and structural relationship to adenylate kinase. Biochemistry. 1988 Jan 26;27(2):553–560. doi: 10.1021/bi00402a008. [DOI] [PubMed] [Google Scholar]
- Gelfand R., Attardi G. Synthesis and turnover of mitochondrial ribonucleic acid in HeLa cells: the mature ribosomal and messenger ribonucleic acid species are metabolically unstable. Mol Cell Biol. 1981 Jun;1(6):497–511. doi: 10.1128/mcb.1.6.497. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gillham N. W., Boynton J. E., Hauser C. R. Translational regulation of gene expression in chloroplasts and mitochondria. Annu Rev Genet. 1994;28:71–93. doi: 10.1146/annurev.ge.28.120194.000443. [DOI] [PubMed] [Google Scholar]
- Grivell L. A. Nucleo-mitochondrial interactions in yeast mitochondrial biogenesis. Eur J Biochem. 1989 Jul 1;182(3):477–493. doi: 10.1111/j.1432-1033.1989.tb14854.x. [DOI] [PubMed] [Google Scholar]
- Groudinsky O., Bousquet I., Wallis M. G., Slonimski P. P., Dujardin G. The NAM1/MTF2 nuclear gene product is selectively required for the stability and/or processing of mitochondrial transcripts of the atp6 and of the mosaic, cox1 and cytb genes in Saccharomyces cerevisiae. Mol Gen Genet. 1993 Sep;240(3):419–427. doi: 10.1007/BF00280396. [DOI] [PubMed] [Google Scholar]
- Hallman M. Changes in mitochondrial respiratory chain proteins during perinatal development. Evidence of the importance of environmental oxygen tension. Biochim Biophys Acta. 1971 Dec 7;253(2):360–372. doi: 10.1016/0005-2728(71)90040-5. [DOI] [PubMed] [Google Scholar]
- Haraguchi Y., Chung A. B., Neill S., Wallace D. C. OXBOX and REBOX, overlapping promoter elements of the mitochondrial F0F1-ATP synthase beta subunit gene. OXBOX/REBOX in the ATPsyn beta promoter. J Biol Chem. 1994 Mar 25;269(12):9330–9334. [PubMed] [Google Scholar]
- Izquierdo J. M., Cuezva J. M. Thyroid hormones promote transcriptional activation of the nuclear gene coding for mitochondrial beta-F1-ATPase in rat liver. FEBS Lett. 1993 May 24;323(1-2):109–112. doi: 10.1016/0014-5793(93)81459-d. [DOI] [PubMed] [Google Scholar]
- Izquierdo J. M., Jiménez E., Cuezva J. M. Hypothyroidism affects the expression of the beta-F1-ATPase gene and limits mitochondrial proliferation in rat liver at all stages of development. Eur J Biochem. 1995 Sep 1;232(2):344–350. doi: 10.1111/j.1432-1033.1995.344zz.x. [DOI] [PubMed] [Google Scholar]
- Izquierdo J. M., Luis A. M., Cuezva J. M. Postnatal mitochondrial differentiation in rat liver. Regulation by thyroid hormones of the beta-subunit of the mitochondrial F1-ATPase complex. J Biol Chem. 1990 Jun 5;265(16):9090–9097. [PubMed] [Google Scholar]
- Izquierdo J. M., Ricart J., Ostronoff L. K., Egea G., Cuezva J. M. Changing patterns of transcriptional and post-transcriptional control of beta-F1-ATPase gene expression during mitochondrial biogenesis in liver. J Biol Chem. 1995 Apr 28;270(17):10342–10350. doi: 10.1074/jbc.270.17.10342. [DOI] [PubMed] [Google Scholar]
- Kim K., Lecordier A., Bowman L. H. Both nuclear and mitochondrial cytochrome c oxidase mRNA levels increase dramatically during mouse postnatal development. Biochem J. 1995 Mar 1;306(Pt 2):353–358. doi: 10.1042/bj3060353. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kruse B., Narasimhan N., Attardi G. Termination of transcription in human mitochondria: identification and purification of a DNA binding protein factor that promotes termination. Cell. 1989 Jul 28;58(2):391–397. doi: 10.1016/0092-8674(89)90853-2. [DOI] [PubMed] [Google Scholar]
- Lansman R. A., Clayton D. A. Mitochondrial protein synthesis in mouse L-cells: effect of selective nicking of mitochondrial DNA. J Mol Biol. 1975 Dec 25;99(4):777–793. doi: 10.1016/s0022-2836(75)80184-7. [DOI] [PubMed] [Google Scholar]
- Luis A. M., Izquierdo J. M., Ostronoff L. K., Salinas M., Santarén J. F., Cuezva J. M. Translational regulation of mitochondrial differentiation in neonatal rat liver. Specific increase in the translational efficiency of the nuclear-encoded mitochondrial beta-F1-ATPase mRNA. J Biol Chem. 1993 Jan 25;268(3):1868–1875. [PubMed] [Google Scholar]
- Montoya J., Gaines G. L., Attardi G. The pattern of transcription of the human mitochondrial rRNA genes reveals two overlapping transcription units. Cell. 1983 Aug;34(1):151–159. doi: 10.1016/0092-8674(83)90145-9. [DOI] [PubMed] [Google Scholar]
- Nagley P. Coordination of gene expression in the formation of mammalian mitochondria. Trends Genet. 1991 Jan;7(1):1–4. doi: 10.1016/0168-9525(91)90002-8. [DOI] [PubMed] [Google Scholar]
- Ojala D., Montoya J., Attardi G. tRNA punctuation model of RNA processing in human mitochondria. Nature. 1981 Apr 9;290(5806):470–474. doi: 10.1038/290470a0. [DOI] [PubMed] [Google Scholar]
- Ostronoff L. K., Izquierdo J. M., Cuezva J. M. mt-mRNA stability regulates the expression of the mitochondrial genome during liver development. Biochem Biophys Res Commun. 1995 Dec 26;217(3):1094–1098. doi: 10.1006/bbrc.1995.2881. [DOI] [PubMed] [Google Scholar]
- Pel H. J., Grivell L. A. Protein synthesis in mitochondria. Mol Biol Rep. 1994 May;19(3):183–194. doi: 10.1007/BF00986960. [DOI] [PubMed] [Google Scholar]
- Polosa P. L., Attardi G. Distinctive pattern and translational control of mitochondrial protein synthesis in rat brain synaptic endings. J Biol Chem. 1991 May 25;266(15):10011–10017. [PubMed] [Google Scholar]
- Rabinovich Y. M., Kreinin M. O. Evidence for non-uniform translation of individual polypeptides in rat liver mitochondria. Biochim Biophys Acta. 1991 Jun 13;1089(2):193–196. doi: 10.1016/0167-4781(91)90007-9. [DOI] [PubMed] [Google Scholar]
- Rohr H. P., Wirz A., Henning L. C., Riede U. N., Bianchi L. Morphometric analysis of the rat liver cell in the perinatal period. Lab Invest. 1971 Feb;24(2):128–139. [PubMed] [Google Scholar]
- Sutton R., Pollak J. K. The increasing adenine nucleotide concentration and the maturation of rat liver mitochondria during neonatal development. Differentiation. 1978 Nov 15;12(1):15–21. doi: 10.1111/j.1432-0436.1979.tb00985.x. [DOI] [PubMed] [Google Scholar]
- Suzuki H., Hosokawa Y., Nishikimi M., Ozawa T. Existence of common homologous elements in the transcriptional regulatory regions of human nuclear genes and mitochondrial gene for the oxidative phosphorylation system. J Biol Chem. 1991 Feb 5;266(4):2333–2338. [PubMed] [Google Scholar]
- Valcarce C., Izquierdo J. M., Chamorro M., Cuezva J. M. Mammalian adaptation to extrauterine environment: mitochondrial functional impairment caused by prematurity. Biochem J. 1994 Nov 1;303(Pt 3):855–862. doi: 10.1042/bj3030855. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Valcarce C., Navarrete R. M., Encabo P., Loeches E., Satrústegui J., Cuezva J. M. Postnatal development of rat liver mitochondrial functions. The roles of protein synthesis and of adenine nucleotides. J Biol Chem. 1988 Jun 5;263(16):7767–7775. [PubMed] [Google Scholar]
- Virbasius C. A., Virbasius J. V., Scarpulla R. C. NRF-1, an activator involved in nuclear-mitochondrial interactions, utilizes a new DNA-binding domain conserved in a family of developmental regulators. Genes Dev. 1993 Dec;7(12A):2431–2445. doi: 10.1101/gad.7.12a.2431. [DOI] [PubMed] [Google Scholar]
- Virbasius J. V., Scarpulla R. C. Activation of the human mitochondrial transcription factor A gene by nuclear respiratory factors: a potential regulatory link between nuclear and mitochondrial gene expression in organelle biogenesis. Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1309–1313. doi: 10.1073/pnas.91.4.1309. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wallace D. C. Diseases of the mitochondrial DNA. Annu Rev Biochem. 1992;61:1175–1212. doi: 10.1146/annurev.bi.61.070192.005523. [DOI] [PubMed] [Google Scholar]
- Wallis M. G., Groudinsky O., Slonimski P. P., Dujardin G. The NAM1 protein (NAM1p), which is selectively required for cox1, cytb and atp6 transcript processing/stabilisation, is located in the yeast mitochondrial matrix. Eur J Biochem. 1994 May 15;222(1):27–32. doi: 10.1111/j.1432-1033.1994.tb18837.x. [DOI] [PubMed] [Google Scholar]
- Williams R. S. Mitochondrial gene expression in mammalian striated muscle. Evidence that variation in gene dosage is the major regulatory event. J Biol Chem. 1986 Sep 15;261(26):12390–12394. [PubMed] [Google Scholar]
- Williams R. S., Salmons S., Newsholme E. A., Kaufman R. E., Mellor J. Regulation of nuclear and mitochondrial gene expression by contractile activity in skeletal muscle. J Biol Chem. 1986 Jan 5;261(1):376–380. [PubMed] [Google Scholar]