Mitochondria and cancer.
Mitochondria contained in cancer cells exhibit two major alterations. First, they are often relatively resistant to the induction of mitochondrial membrane permeabilization (MMP), which is the rate-limiting step of the intrinsic pathway of apoptosis. The mechanisms of MMP resistance have come under close scrutiny because apoptosis resistance constitutes one of the essential hallmarks of cancer. Second, cancer cell mitochondria often exhibit a reduced oxidative phosphorylation, meaning that ATP is generated through the conversion of glucose to pyruvate and excess pyruvate is then eliminated as the waste product lactate. This glycolytic mode of energy production is even observed in conditions of high oxygen tension and is hence called anaerobic glycolysis. Here, we discuss the molecular mechanisms accounting for inhibition of the mitochondrial apoptosis pathway in neoplasia and discuss possible mechanistic links between MMP resistance and anaerobic glycolysis.
Rustin
P
P
INSERM, U676, Hopital Robert Debre, Paris, France.
Kroemer
G
G
D000693:Anaerobiosis; D000818:Animals; D017209:Apoptosis; D006019:Glycolysis; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010085:Oxidative Phosphorylation; D010539:Permeability