Mitochondrial survivin reduces oxidative phosphorylation in cancer cells by inhibiting mitophagy

Amelia R Townley1, Sally P Wheatley2

  • 1School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK.

Journal of Cell Science
|October 20, 2020
PubMed

Insights

Mitochondrial survivin protein inhibits mitophagy, leading to defective mitochondria accumulation in cancer cells. This process promotes cancer cell adaptation and survival by increasing reliance on glycolysis.

Area of Science:

  • Cell Biology
  • Cancer Biology
  • Biochemistry

Background:

  • Survivin (BIRC5) is a key protein regulating cell death and mitosis.
  • A subset of survivin localizes to mitochondria in cancer cells, with its function unclear.
  • Autophagy, particularly mitophagy, is crucial for mitochondrial quality control.

Purpose of the Study:

  • To investigate the role of mitochondrial survivin in cancer cells.
  • To elucidate the mechanism by which mitochondrial survivin affects cellular processes.
  • To understand the implications of mitochondrial survivin's function for cancer metabolism and survival.

Main Methods:

  • Investigated survivin's localization and function in cancer cells.
  • Utilized techniques to study mitophagy and mitochondrial function.
  • Analyzed cellular metabolic changes, including glycolysis and mitochondrial respiration.

Main Results:

  • Mitochondrial survivin was found to inhibit mitophagy, preventing the removal of damaged mitochondria.
  • Survivin blocks the recruitment of Parkin to mitochondria, a key step in mitophagy.
  • Inhibition of mitophagy by survivin leads to an accumulation of dysfunctional mitochondria and increased glycolysis.
  • These effects were specific to cancer cells.

Conclusions:

  • Mitochondrial survivin plays a critical role in cancer cell adaptation by inhibiting mitophagy.
  • This inhibition promotes metabolic reprogramming towards glycolysis (Warburg effect).
  • Survivin's action on mitophagy provides a mechanism for cancer cells to survive and adapt by maintaining dysfunctional mitochondria.

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