YME1L controls the accumulation of respiratory chain subunits and is required for apoptotic resistance, cristae morphogenesis, and cell proliferation
| Autor: | Jiri Zeman, Daniela Fornuskova, Kamila Vinsova, Lukas Stiburek, Laszlo Wenchich, Olga Kostkova, Josef Houstek, Jana Cesnekova |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Saccharomyces cerevisiae Proteins
medicine.medical_treatment Biosynthesis and Biodegradation Saccharomyces cerevisiae Morphogenesis Respiratory chain Apoptosis Mitochondrion GTP Phosphohydrolases Electron Transport Electron Transport Complex IV Mitochondrial Proteins ATP-Dependent Proteases medicine Humans Protein Isoforms NADH NADPH Oxidoreductases Molecular Biology Cell Proliferation Electron Transport Complex I Protease biology Cell growth Metalloendopeptidases Articles Cell Biology biology.organism_classification Molecular biology Mitochondria Cell biology Gene Knockdown Techniques Mitochondrial Membranes ATPases Associated with Diverse Cellular Activities Peptide Hydrolases |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e11-08-0674 |
| Popis: | Loss-of-function studies show that the human mitochondrial YME1L protease ensures cell proliferation, maintains normal cristae morphology and complex I activity, acts in an antiapoptotic manner, protects mitochondria from accumulation of oxidatively damaged membrane proteins, and is involved in proteolytic regulation of respiratory chain biogenesis. 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|