Mitochondria and cancer.

P Rustin, G Kroemer
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引用次数: 10

Abstract

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.

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线粒体和癌症。
癌细胞中的线粒体表现出两个主要的变化。首先,它们通常相对抵抗线粒体膜透性(MMP)的诱导,而线粒体膜透性是细胞凋亡内在途径的限速步骤。由于细胞凋亡抵抗是癌症的基本特征之一,因此MMP耐药的机制一直受到密切关注。其次,癌细胞线粒体经常表现出氧化磷酸化的减少,这意味着ATP是通过葡萄糖转化为丙酮酸而产生的,多余的丙酮酸随后作为乳酸废物被消除。这种能量产生的糖酵解模式甚至在高氧张力条件下也能观察到,因此被称为厌氧糖酵解。在这里,我们讨论了肿瘤中线粒体凋亡途径抑制的分子机制,并讨论了MMP耐药性与厌氧糖酵解之间可能的机制联系。
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