Journal
BIOLOGICAL CHEMISTRY
Volume 402, Issue 1, Pages 73-88Publisher
WALTER DE GRUYTER GMBH
DOI: 10.1515/hsz-2020-0231
Keywords
BCL-2 family; caspase-3; Parkin; Parkinson's disease; PINK1; synaptic plasticity
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Funding
- Else Kroner-Fresenius-Stiftung
- Max-Planck-Gesellschaft
- Deutsche Forschungsgemeinschaft [CIBSS - EXC-2189, 390939984]
- Heisenberg Program, Munich Cluster for Systems Neurology
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Mitochondria are crucial for cellular metabolism, Ca2+ homeostasis, and apoptosis. Mitophagy helps cells cope with mitochondrial stress until damage becomes too great, leading to activation of proapoptotic proteins and initiation of apoptosis. The choice between mitophagy and caspase activation in neurons also plays a role in synaptic plasticity.
Mitochondria are key players of cellular metabolism, Ca2+ homeostasis, and apoptosis. The functionality of mitochondria is tightly regulated, and dysfunctional mitochondria are removed via mitophagy, a specialized form of autophagy that is compromised in hereditary forms of Parkinson's disease. Through mitophagy, cells are able to cope with mitochondrial stress until the damage becomes too great, which leads to the activation of proapoptotic BCL-2 family proteins located on the outer mitochondrial membrane. Active pro-apoptotic BCL-2 proteins facilitate the release of cytochrome c from the mitochondrial intermembrane space (IMS) into the cytosol, committing the cell to apoptosis by activating a cascade of cysteinyl-aspartate specific proteases (caspases). We are only beginning to understand how the choice between mitophagy and the activation of caspases is determined on the mitochondrial surface. Intriguingly in neurons, caspase activation also plays a non-apoptotic role in synaptic plasticity. Here we review the current knowledge on the interplay between mitophagy and caspase activation with a special focus on the central nervous system.
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