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Review
. 2020 Oct 12;402(1):73-88.
doi: 10.1515/hsz-2020-0231. Print 2020 Nov 18.

Kill one or kill the many: interplay between mitophagy and apoptosis

Simone Wanderoy  1 , J Tabitha Hees  1 , Ramona Klesse  2   3 , Frank Edlich  2 , Angelika B Harbauer  1   4   5
Affiliations
Free article
Review

Kill one or kill the many: interplay between mitophagy and apoptosis

Simone Wanderoy et al. Biol Chem. .
Free article

Abstract

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 pro-apoptotic 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.

Keywords: BCL-2 family; PINK1; Parkin; Parkinson’s disease; caspase-3; synaptic plasticity.

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