Reference - Detail
| RRC ID | 48899 |
|---|---|
| Author | Meng H, Yamashita C, Shiba-Fukushima K, Inoshita T, Funayama M, Sato S, Hatta T, Natsume T, Umitsu M, Takagi J, Imai Y, Hattori N. |
| Title | Loss of Parkinson's disease-associated protein CHCHD2 affects mitochondrial crista structure and destabilizes cytochrome c. |
| Journal | Nat Commun |
| Abstract |
Mutations in CHCHD2 have been identified in some Parkinson's disease (PD) cases. To understand the physiological and pathological roles of CHCHD2, we manipulated the expression of CHCHD2 in Drosophila and mammalian cells. The loss of CHCHD2 in Drosophila causes abnormal matrix structures and impaired oxygen respiration in mitochondria, leading to oxidative stress, dopaminergic neuron loss and motor dysfunction with age. These PD-associated phenotypes are rescued by the overexpression of the translation inhibitor 4E-BP and by the introduction of human CHCHD2 but not its PD-associated mutants. CHCHD2 is upregulated by various mitochondrial stresses, including the destabilization of mitochondrial genomes and unfolded protein stress, in Drosophila. CHCHD2 binds to cytochrome c along with a member of the Bax inhibitor-1 superfamily, MICS1, and modulated cell death signalling, suggesting that CHCHD2 dynamically regulates the functions of cytochrome c in both oxidative phosphorylation and cell death in response to mitochondrial stress. |
| Volume | 8 |
| Pages | 15500 |
| Published | 2017-6-7 |
| DOI | 10.1038/ncomms15500 |
| PII | ncomms15500 |
| PMID | 28589937 |
| PMC | PMC5467237 |
| MeSH | Adaptor Proteins, Signal Transducing / metabolism Animals Cell Survival Cytochromes c / metabolism* DNA-Binding Proteins Dopaminergic Neurons / metabolism Dopaminergic Neurons / pathology Drosophila Proteins / metabolism* Drosophila melanogaster / metabolism* Drosophila melanogaster / ultrastructure Electron Transport Flight, Animal / physiology Humans Male Mice Mitochondria / metabolism* Mitochondria / ultrastructure Mitochondrial Proteins / metabolism* Models, Biological Muscles / ultrastructure Mutation / genetics Nerve Degeneration / pathology Oxidative Phosphorylation Oxidative Stress Parkinson Disease / genetics Parkinson Disease / pathology* Phenotype Protein Binding Protein Stability Signal Transduction Stress, Physiological Transcription Factors / metabolism* Ubiquitin-Protein Ligases / metabolism Up-Regulation |
| IF | 12.121 |
| Times Cited | 33 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Resource | |
| Human and Animal Cells | HeLa 293T(RCB2202) |
| Drosophila | |