FIGURE 4.

Regulation of mGSH by mitochondrial cholesterol loading in health and disease. (A) In healthy mitochondria, mGSH levels can cope with the ROS generated in physiological conditions, avoiding cell death induction and maintenance of mitochondrial functions. (B) In cholesterol-enriched mitochondria, the mGSH transport is impaired resulting in mGSH depletion. mGSH levels below a certain threshold compromise ROS detoxification, leading to oxidative stress and resulting ultimately in higher susceptibility to cell death. (C) However, cancer cells exhibit increased cholesterol enrichment of mitochondrial membrane but paradoxically maintain mGSH levels despite changes in membrane physical properties by an as yet uncharacterized mechanism. Increased mitochondrial cholesterol and mGSH protect against mitochondrial membrane permeabilization and cell death. Thus, targeting mitochondrial cholesterol or mGSH may be a novel approach in the treatment of cancer.