A new function in translocation for the mitochondrial i-AAA protease Yme1: import of polynucleotide phosphorylase into the intermembrane space.
Polynucleotide phosphorylase (PNPase) is an exoribonuclease and poly(A) polymerase postulated to function in the cytosol and mitochondrial matrix. Prior overexpression studies resulted in PNPase localization to both the cytosol and mitochondria, concurrent with cytosolic RNA degradation and pleiotropic cellular effects, including growth inhibition and apoptosis, that may not reflect a physiologic role for endogenous PNPase. We therefore conducted a mechanistic study of PNPase biogenesis in the mitochondrion. Interestingly, PNPase is localized to the intermembrane space by a novel import pathway. PNPase has a typical N-terminal targeting sequence that is cleaved by the matrix processing peptidase when PNPase engaged the TIM23 translocon at the inner membrane. The i-AAA protease Yme1 mediated translocation of PNPase into the intermembrane space but did not degrade PNPase. In a yeast strain deleted for Yme1 and expressing PNPase, nonimported PNPase accumulated in the cytosol, confirming an in vivo role for Yme1 in PNPase maturation. PNPase localization to the mitochondrial intermembrane space suggests a unique role distinct from its highly conserved function in RNA processing in chloroplasts and bacteria. Furthermore, Yme1 has a new function in protein translocation, indicating that the intermembrane space harbors diverse pathways for protein translocation.
Rainey
Robert N
RN
Department of Chemistry and Biochemistry, UCLA, Los Angeles, CA 90095-1569, USA.
Glavin
Jenny D
JD
Chen
Hsiao-Wen
HW
French
Samuel W
SW
Teitell
Michael A
MA
Koehler
Carla M
CM
D049069:ATP-Dependent Proteases; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008666:Metalloendopeptidases / Q000737:chemistry; D008928:Mitochondria / Q000201:enzymology*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008954:Models, Biological; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000502:physiology; D011117:Polyribonucleotide Nucleotidyltransferase / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism; D014178:Translocation, Genetic; D000096122:Mitochondrial Processing Peptidase
D049069:ATP-Dependent Proteases; D000251:Adenosine Triphosphatases; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D008666:Metalloendopeptidases; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D010447:Peptide Hydrolases; D011117:Polyribonucleotide Nucleotidyltransferase; D029701:Saccharomyces cerevisiae Proteins; D013762:Tetrahydrofolate Dehydrogenase; D000096122:Mitochondrial Processing Peptidase; C083081:TIM23 protein, S cerevisiae; C082702:YME1 protein, S cerevisiae