| First Author | Lu W | Year | 2014 |
| Journal | Nat Commun | Volume | 5 |
| Pages | 4930 | PubMed ID | 25222142 |
| Mgi Jnum | J:225345 | Mgi Id | MGI:5692409 |
| Doi | 10.1038/ncomms5930 | Citation | Lu W, et al. (2014) Genetic deficiency of the mitochondrial protein PGAM5 causes a Parkinson's-like movement disorder. Nat Commun 5:4930 |
| abstractText | Mitophagy is a specialized form of autophagy that selectively disposes of dysfunctional mitochondria. Delineating the molecular regulation of mitophagy is of great importance because defects in this process lead to a variety of mitochondrial diseases. Here we report that mice deficient for the mitochondrial protein, phosphoglycerate mutase family member 5 (PGAM5), displayed a Parkinson's-like movement phenotype. We determined biochemically that PGAM5 is required for the stabilization of the mitophagy-inducing protein PINK1 on damaged mitochondria. Loss of PGAM5 disables PINK1-mediated mitophagy in vitro and leads to dopaminergic neurodegeneration and mild dopamine loss in vivo. Our data indicate that PGAM5 is a regulator of mitophagy essential for mitochondrial turnover and serves a cytoprotective function in dopaminergic neurons in vivo. Moreover, PGAM5 may provide a molecular link to study mitochondrial homeostasis and the pathogenesis of a movement disorder similar to Parkinson's disease. |
