Mitochondrial ATPases associated with diverse cellular activities (AAA) proteases are involved in the quality control and processing of inner-membrane proteins. Here we investigate the cellular activities of YME1L, the human orthologue of the Yme1 subunit of the yeast i-AAA complex, using stable short hairpin RNA knockdown and expression experiments. Human YME1L is shown to be an integral membrane protein that exposes its carboxy-terminus to the intermembrane space and exists in several complexes of 600-1100 kDa. The stable knockdown of YME1L in human embryonic kidney 293 cells led to impaired cell proliferation and apoptotic resistance, altered cristae morphology, diminished rotenone-sensitive respiration, and increased susceptibility to mitochondrial membrane protein carbonylation. Depletion of YME1L led to excessive accumulation of nonassembled respiratory chain subunits (Ndufb6, ND1, and Cox4) in the inner membrane. This was due to a lack of YME1L proteolytic activity, since the excessive accumulation of subunits was reversed by overexpression of wild-type YME1L but not a proteolytically inactive YME1L variant. Similarly, the expression of wild-type YME1L restored the lamellar cristae morphology of YME1L-deficient mitochondria. Our results demonstrate the importance of mitochondrial inner-membrane proteostasis to both mitochondrial and cellular function and integrity and reveal a novel role for YME1L in the proteolytic regulation of respiratory chain biogenesis.

• MeSH
• apoptóza MeSH
• ATPázy spojené s různými buněčnými aktivitami MeSH
• genový knockdown MeSH
• GTP-fosfohydrolasy metabolismus   MeSH
• lidé MeSH
• metaloendopeptidasy metabolismus   MeSH
• mitochondriální membrány metabolismus   MeSH
• mitochondriální proteiny MeSH
• mitochondrie metabolismus   MeSH
• NADH, NADPH oxidoreduktasy metabolismus   MeSH
• proliferace buněk * MeSH
• proteasy závislé na ATP metabolismus   MeSH
• proteasy metabolismus   MeSH
• protein - isoformy metabolismus   MeSH
• respirační komplex I MeSH
• respirační komplex IV metabolismus   MeSH
• Saccharomyces cerevisiae - proteiny metabolismus   MeSH
• Saccharomyces cerevisiae cytologie   metabolismus   MeSH
• transport elektronů * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ATPázy spojené s různými buněčnými aktivitami MeSH
• GTP-fosfohydrolasy MeSH
• metaloendopeptidasy MeSH
• mitochondriální proteiny MeSH
• NADH, NADPH oxidoreduktasy MeSH
• NDUFB6 protein, human MeSH Prohlížeč
• OPA1 protein, human MeSH Prohlížeč
• proteasy závislé na ATP MeSH
• proteasy MeSH
• protein - isoformy MeSH
• respirační komplex I MeSH
• respirační komplex IV MeSH
• Saccharomyces cerevisiae - proteiny MeSH
• YME1 protein, S cerevisiae MeSH Prohlížeč
• YME1L1 protein, human MeSH Prohlížeč