Mol Cell 2016[Mar]; 61 (5): 667-76 PMID26942671show ga
Decades ago Otto Warburg observed that cancers ferment glucose in the presence of oxygen, suggesting that defects in mitochondrial respiration may be the underlying cause of cancer. We now know that the genetic events, which drive aberrant cancer cell proliferation, also alter biochemical metabolism including promoting aerobic glycolysis, but do not typically impair mitochondrial function. Mitochondria supply energy, provide building blocks for new cells, and control redox homeostasis, oncogenic signaling, innate immunity and apoptosis. Indeed, mitochondrial biogenesis and quality control are often upregulated in cancers. While some cancers have mutations in nuclear-encoded mitochondrial tricarboxylic acid (TCA) cycle enzymes that produce oncogenic metabolites, there is negative selection for pathogenic mitochondrial genome mutations. Eliminating mitochondrial DNA limits tumorigenesis and rare human tumors with mutant mitochondrial genomes are relatively benign. Thus, mitochondria play a central and multi-functional role in malignant tumor progression, and targeting mitochondria provides therapeutic opportunities.
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Mol+Cell 2016 ; 61 (5): 667-76
