First Author | Lin MY | Year | 2017 |
Journal | Neuron | Volume | 94 |
Issue | 3 | Pages | 595-610.e6 |
PubMed ID | 28472658 | Mgi Jnum | J:242554 |
Mgi Id | MGI:5905578 | Doi | 10.1016/j.neuron.2017.04.004 |
Citation | Lin MY, et al. (2017) Releasing Syntaphilin Removes Stressed Mitochondria from Axons Independent of Mitophagy under Pathophysiological Conditions. Neuron 94(3):595-610.e6 |
abstractText | Chronic mitochondrial stress is a central problem associated with neurodegenerative diseases. Early removal of defective mitochondria from axons constitutes a critical step of mitochondrial quality control. Here we investigate axonal mitochondrial response to mild stress in wild-type neurons and chronic mitochondrial defects in Amytrophic Lateral Sclerosis (ALS)- and Alzheimer's disease (AD)-linked neurons. We show that stressed mitochondria are removed from axons triggered by the bulk release of mitochondrial anchoring protein syntaphilin via a new class of mitochondria-derived cargos independent of Parkin, Drp1, and autophagy. Immuno-electron microscopy and super-resolution imaging show the budding of syntaphilin cargos, which then share a ride on late endosomes for transport toward the soma. Releasing syntaphilin is also activated in the early pathological stages of ALS- and AD-linked mutant neurons. Our study provides new mechanistic insights into the maintenance of axonal mitochondrial quality through SNPH-mediated coordination of mitochondrial stress and motility before activation of Parkin-mediated mitophagy. VIDEO ABSTRACT. |