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Mitochondrial survivin reduces oxidative phosphorylation in cancer cells by inhibiting mitophagy.

Wheatley, Sally; Townley, Amelia R

Mitochondrial survivin reduces oxidative phosphorylation in cancer cells by inhibiting mitophagy. Thumbnail


Authors

Amelia R Townley



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.

Citation

Wheatley, S., & Townley, A. R. Mitochondrial survivin reduces oxidative phosphorylation in cancer cells by inhibiting mitophagy

Other Type Other
Deposit Date Apr 27, 2020
Publicly Available Date Mar 29, 2024
DOI https://doi.org/10.1101/2020.04.21.052662
Public URL https://nottingham-repository.worktribe.com/output/4341439
Additional Information This is a preprint in BioRxiv.

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