| First Author | Korwitz A | Year | 2016 |
| Journal | J Cell Biol | Volume | 212 |
| Issue | 2 | Pages | 157-66 |
| PubMed ID | 26783299 | Mgi Jnum | J:230824 |
| Mgi Id | MGI:5766104 | Doi | 10.1083/jcb.201507022 |
| Citation | Korwitz A, et al. (2016) Loss of OMA1 delays neurodegeneration by preventing stress-induced OPA1 processing in mitochondria. J Cell Biol 212(2):157-66 |
| abstractText | Proteolytic cleavage of the dynamin-like guanosine triphosphatase OPA1 in mitochondria is emerging as a central regulatory hub that determines mitochondrial morphology under stress and in disease. Stress-induced OPA1 processing by OMA1 triggersmitochondrial fragmentation, which is associated with mitophagy and apoptosis in vitro. Here, we identify OMA1 as a critical regulator of neuronal survival in vivo and demonstrate that stress-induced OPA1 processing by OMA1 promotes neuronal death and neuroinflammatory responses. Using mice lacking prohibitin membrane scaffolds as a model of neurodegeneration, we demonstrate that additional ablation of Oma1 delays neuronal loss and prolongs lifespan. This is accompanied by the accumulation of fusion-active, long OPA1 forms, which stabilize the mitochondrial genome but do not preserve mitochondrial cristae or respiratory chain supercomplex assembly in prohibitin-depleted neurons. Thus, long OPA1 forms can promote neuronal survival independently of cristae shape, whereas stress-induced OMA1 activation and OPA1 cleavage limit mitochondrial fusion and promote neuronal death. |
