論文 - 詳細
| RRC ID | 46177 |
|---|---|
| 著者 | Rolland SG, Motori E, Memar N, Hench J, Frank S, Winklhofer KF, Conradt B. |
| タイトル | Impaired complex IV activity in response to loss of LRPPRC function can be compensated by mitochondrial hyperfusion. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
Mitochondrial morphology changes in response to various stimuli but the significance of this is unclear. In a screen for mutants with abnormal mitochondrial morphology, we identified MMA-1, the Caenorhabditis elegans homolog of the French Canadian Leigh Syndrome protein LRPPRC (leucine-rich pentatricopeptide repeat containing). We demonstrate that reducing mma-1 or LRPPRC function causes mitochondrial hyperfusion. Reducing mma-1/LRPPRC function also decreases the activity of complex IV of the electron transport chain, however without affecting cellular ATP levels. Preventing mitochondrial hyperfusion in mma-1 animals causes larval arrest and embryonic lethality. Furthermore, prolonged LRPPRC knock-down in mammalian cells leads to mitochondrial fragmentation and decreased levels of ATP. These findings indicate that in a mma-1/LRPPRC-deficient background, hyperfusion allows mitochondria to maintain their functions despite a reduction in complex IV activity. Our data reveal an evolutionary conserved mechanism that is triggered by reduced complex IV function and that induces mitochondrial hyperfusion to transiently compensate for a drop in the activity of the electron transport chain. |
| 巻・号 | 110(32) |
| ページ | E2967-76 |
| 公開日 | 2013-8-6 |
| DOI | 10.1073/pnas.1303872110 |
| PII | 1303872110 |
| PMID | 23878239 |
| PMC | PMC3740885 |
| MeSH | Adenosine Triphosphate / metabolism Animals Animals, Genetically Modified Blotting, Western Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Cell Line Cell Line, Tumor DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Electron Transport Complex IV / metabolism* GTP Phosphohydrolases / genetics GTP Phosphohydrolases / metabolism Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism Humans Leigh Disease / genetics Leigh Disease / metabolism Leigh Disease / pathology Membrane Proteins / genetics Membrane Proteins / metabolism Microscopy, Fluorescence Mitochondria / genetics Mitochondria / metabolism* Mitochondrial Proteins / genetics Mitochondrial Proteins / metabolism* Molecular Chaperones Neoplasm Proteins / genetics Neoplasm Proteins / metabolism* RNA Interference Transcription Factors / genetics Transcription Factors / metabolism |
| IF | 9.412 |
| 引用数 | 35 |
| WOS 分野 | CELL BIOLOGY |
| リソース情報 | |
| 線虫 | tm1133 tm1107 tm1108 |