Handling Editor: Daniel Billadeau
ABSTRACT
Survivin (also known as BIRC5) 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 cells in which mitophagy has been blocked by survivin expression have an increased dependency on glycolysis. As these effects were found exclusively in cancer cells, they suggest that the primary act of mitochondrial survivin is to steer cells towards the implementation of the Warburg transition by inhibiting mitochondrial turnover, which enables them to adapt and survive.
This article has an associated First Person interview with the first author of the paper.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: A.R.T., S.P.W.; Methodology: A.R.T., S.P.W.; Validation: A.R.T., S.P.W.; Investigation: S.P.W.; Data curation: A.R.T.; Writing - original draft: A.R.T.; Writing - review & editing: S.P.W.; Visualization: A.R.T., S.P.W.; Supervision: S.P.W.; Project administration: S.P.W.; Funding acquisition: S.P.W.
Funding
A.R.T. was supported by a Biotechnology and Biological Sciences Research Council studentship.
Supplementary information
Supplementary information available online at https://jcs.biologists.org/lookup/doi/10.1242/jcs.247379.supplemental
- Received April 21, 2020.
- Accepted September 29, 2020.
- © 2020. Published by The Company of Biologists Ltd
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