Involvement of cytochrome c oxidase subunits Va and Vb in the regulation of cancer cell metabolism by Bcl-2
- 16 October 2009
- journal article
- Published by Springer Science and Business Media LLC in Cell Death & Differentiation
- Vol. 17 (3), 408-420
- https://doi.org/10.1038/cdd.2009.132
Abstract
Bcl-2 has been shown to promote survival of cancer cells by maintaining a slight pro-oxidant state through elevated mitochondrial respiration during basal conditions. On oxidative stress, Bcl-2 moderates mitochondrial respiration through cytochrome c oxidase (COX) activity to prevent an excessive buildup of reactive oxygen species (ROS) by-production from electron transport activities. However, the underlying molecular mechanism(s) of Bcl-2-mediated ROS regulation and its impact on carcinogenesis remain unclear. In this study, we show that Bcl-2 expression positively influences the targeting of nuclear-encoded COX Va and Vb to the mitochondria of cancer cells. In addition, evidence is presented in support of a protein–protein interaction between COX Va and Bcl-2, involving the BH2 domain of Bcl-2. Interestingly, episodes of serum withdrawal, glucose deprivation or hypoxia aimed at inducing early oxidative stress triggered Bcl-2-overexpressing cells to preserve mitochondrial levels of COX Va while depressing COX Vb, whereas the reverse was observed in mock-transfected cells. The unique manner in which Bcl-2 adjusted COX subunits during these physiological stress triggers had a profound impact on the resultant decrease in COX activity and maintenance of mitochondrial ROS levels, thus delineating a novel mechanism for the homeostatic role of Bcl-2 in the redox biology and metabolism of cancer cells.This publication has 35 references indexed in Scilit:
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