| Autor: |
Killackey SA; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada., Bi Y; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada., Philpott DJ; Department of Immunology, University of Toronto, Toronto, ON, Canada., Arnoult D; INSERM U1197, Hôpital Paul Brousse, Bâtiment Lavoisier, Villejuif Cedex, France., Girardin SE; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.; Department of Immunology, University of Toronto, Toronto, ON, Canada. |
| Abstrakt: |
Mitochondria rely on efficient protein import across their membranes for optimal function. We have shown that numerous mitochondrial stressors all converge on a common pathway disrupting this import efficiency. We identified a novel pathway involving NLRX1 and RRBP1 that responds to this import stress, resulting in LC3 lipidation, mitochondrial targeting and ultimate degradation. Furthermore, we demonstrated the relevance of this mitophagy axis in murine skeletal muscle following acute exercise. We propose that mitochondrial protein import stress is an underlying, common trigger for mitophagy, offering a novel avenue for therapeutic exploration and mechanistic insight. |
