Mitochondrial survivin reduces oxidative phosphorylation in cancer cells by inhibiting mitophagy

Townley, Amelia; Wheatley, Sally P.

Abstract

Survivin is a cancer-associated protein that is pivotal for cellular life and death: it is an essential mitotic protein and an inhibitor of apoptosis. In cancer cells, a small pool of survivin localises to the mitochondria, the function of which remains to be elucidated. Here, we report that mitochondrial survivin inhibits the selective form of autophagy, called “mitophagy”, causing an accumulation of respiratory defective mitochondria. Mechanistically the data reveal that survivin prevents recruitment of the E3-ubiquitin ligase Parkin to mitochondria and their subsequent recognition by the autophagosome. The data also demonstrate that as a consequence of this blockade cells expressing high levels of survivin have an increased dependency on anaerobic glycolysis. As these effects were found exclusively in cancer cells they suggest that the primary act of mitochondrial survivin is to force cells to implement the “Warburg Effect” by inhibiting mitochondrial turnover, which gives them a survival advantage.

Citation

Townley, A., & Wheatley, S. P. (2020). Mitochondrial survivin reduces oxidative phosphorylation in cancer cells by inhibiting mitophagy. Journal of Cell Science, 133(21), Article jcs247379. https://doi.org/10.1242/jcs.247379

• Journal Article Type: Article
• Acceptance Date: Sep 29, 2020
• Online Publication Date: Oct 18, 2020
• Publication Date: Nov 1, 2020
• Deposit Date: Dec 15, 2020
• Publicly Available Date: Oct 19, 2021
• Journal: Journal of Cell Science
• Print ISSN: 0021-9533
• Electronic ISSN: 1477-9137
• Publisher: Company of Biologists
• Peer Reviewed: Peer Reviewed
• Volume: 133
• Issue: 21
• Article Number: jcs247379
• DOI: https://doi.org/10.1242/jcs.247379
• Keywords: Cell Biology
• Public URL: https://nottingham-repository.worktribe.com/output/4934555
• Publisher URL: https://jcs.biologists.org/content/133/21/jcs247379