The ATP-dependent PIM1 Protease is Required for the Expression of Intron-containing Genes in Mitochondria

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 1998 May 29

PMID 9585511

Citations 26

Authors

L Van Dyck

W Neupert

T Langer

Affiliations

Soon will be listed here.

Abstract

The ATP-dependent PIM1 protease, a Lon-like protease localized in the mitochondrial matrix, is required for mitochondrial genome integrity in yeast. Cells lacking PIM1 accumulate lesions in the mitochondrial DNA (mtDNA) and therefore lose respiratory competence. The identification of a multicopy suppressor, which stabilizes mtDNA in the absence of PIM1, enabled us to characterize novel functions of PIM1 protease during mitochondrial biogenesis. The synthesis of mitochondrially encoded cytochrome c oxidase subunit I (CoxI) and cytochrome b (Cob) is impaired in pim1 mutants containing mtDNA. PIM1-mediated proteolysis is required for the translation of mature COXI mRNA. Moreover, deficiencies in the splicing of COXI and COB transcripts, which appear to be restricted to introns encoding mRNA maturases, were observed in cells lacking the PIM1 gene. Transcripts of COXI and COB genes harboring multiple introns are degraded in the absence of PIM1. These results establish multiple, essential functions of the ATP-dependent PIM1 protease during mitochondrial gene expression.

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References

Golik P, Szczepanek T, Bartnik E, Stepien P, Lazowska J . The S. cerevisiae nuclear gene SUV3 encoding a putative RNA helicase is necessary for the stability of mitochondrial transcripts containing multiple introns. Curr Genet. 1995; 28(3):217-24. DOI: 10.1007/BF00309780. View

Langer T, Pajic A, Wagner I, Neupert W . Proteolytic breakdown of membrane-associated polypeptides in mitochondria of Saccharomyces cerevisiae. Methods Enzymol. 1995; 260:495-503. DOI: 10.1016/0076-6879(95)60161-9. View

Guzelin E, Rep M, Grivell L . Afg3p, a mitochondrial ATP-dependent metalloprotease, is involved in degradation of mitochondrially-encoded Cox1, Cox3, Cob, Su6, Su8 and Su9 subunits of the inner membrane complexes III, IV and V. FEBS Lett. 1996; 381(1-2):42-6. DOI: 10.1016/0014-5793(96)00074-9. View

Finke K, Plath K, Panzner S, Prehn S, Rapoport T, Hartmann E . A second trimeric complex containing homologs of the Sec61p complex functions in protein transport across the ER membrane of S. cerevisiae. EMBO J. 1996; 15(7):1482-94. PMC: 450055. View

Teichmann U, Van Dyck L, Guiard B, Fischer H, Glockshuber R, Neupert W . Substitution of PIM1 protease in mitochondria by Escherichia coli Lon protease. J Biol Chem. 1996; 271(17):10137-42. DOI: 10.1074/jbc.271.17.10137. View

ARLT H, Tauer R, Feldmann H, Neupert W, Langer T . The YTA10-12 complex, an AAA protease with chaperone-like activity in the inner membrane of mitochondria. Cell. 1996; 85(6):875-85. DOI: 10.1016/s0092-8674(00)81271-4. View

Adam Z . Protein stability and degradation in chloroplasts. Plant Mol Biol. 1996; 32(5):773-83. DOI: 10.1007/BF00020476. View

Langer T, Neupert W . Regulated protein degradation in mitochondria. Experientia. 1996; 52(12):1069-76. DOI: 10.1007/BF01952104. View

Conde J, Fink G . A mutant of Saccharomyces cerevisiae defective for nuclear fusion. Proc Natl Acad Sci U S A. 1976; 73(10):3651-5. PMC: 431176. DOI: 10.1073/pnas.73.10.3651. View

10.

Douglas M, Finkelstein D, Butow R . Analysis of products of mitochondrial protein synthesis in yeast: genetic and biochemical aspects. Methods Enzymol. 1979; 56:58-66. DOI: 10.1016/0076-6879(79)56009-1. View

11.

Broach J, Strathern J, Hicks J . Transformation in yeast: development of a hybrid cloning vector and isolation of the CAN1 gene. Gene. 1979; 8(1):121-33. DOI: 10.1016/0378-1119(79)90012-x. View

12.

Nobrega F, Tzagoloff A . Assembly of the mitochondrial membrane system. DNA sequence and organization of the cytochrome b gene in Saccharomyces cerevisiae D273-10B. J Biol Chem. 1980; 255(20):9828-37. View

13.

Dhawale S, Hanson D, Alexander N, Perlman P, Mahler H . Regulatory interactions between mitochondrial genes: interactions between two mosaic genes. Proc Natl Acad Sci U S A. 1981; 78(3):1778-82. PMC: 319217. DOI: 10.1073/pnas.78.3.1778. View

14.

McKee E, Poyton R . Mitochondrial gene expression in saccharomyces cerevisiae. I. Optimal conditions for protein synthesis in isolated mitochondria. J Biol Chem. 1984; 259(14):9320-31. View

15.

Yaffe M, Schatz G . Two nuclear mutations that block mitochondrial protein import in yeast. Proc Natl Acad Sci U S A. 1984; 81(15):4819-23. PMC: 391582. DOI: 10.1073/pnas.81.15.4819. View

16.

Butow R, Perlman P, Grossman L . The unusual varl gene of yeast mitochondrial DNA. Science. 1985; 228(4707):1496-501. DOI: 10.1126/science.2990030. View

17.

Tzagoloff A, Myers A . Genetics of mitochondrial biogenesis. Annu Rev Biochem. 1986; 55:249-85. DOI: 10.1146/annurev.bi.55.070186.001341. View

18.

McEwen J, Ko C, Poyton R . Nuclear functions required for cytochrome c oxidase biogenesis in Saccharomyces cerevisiae. Characterization of mutants in 34 complementation groups. J Biol Chem. 1986; 261(25):11872-9. View

19.

Banroques J, Perea J, Jacq C . Efficient splicing of two yeast mitochondrial introns controlled by a nuclear-encoded maturase. EMBO J. 1987; 6(4):1085-91. PMC: 553506. DOI: 10.1002/j.1460-2075.1987.tb04862.x. View

20.

Seraphin B, Boulet A, Simon M, Faye G . Construction of a yeast strain devoid of mitochondrial introns and its use to screen nuclear genes involved in mitochondrial splicing. Proc Natl Acad Sci U S A. 1987; 84(19):6810-4. PMC: 299174. DOI: 10.1073/pnas.84.19.6810. View