Mitochondrial contributions to cancer cell physiology: potential for drug development

Mitochondria make an integral contribution to the regulation of several asp ects of cell biology such as energy production, molecular metabolism, redox status, calcium signaling and programmed cell death. In accordance with an endosymbiotic origin, mitochondria rely upon the nucleus for synthesis and function. In addition, these organelles can respond to intra- and extracel lular cues independently, and there exists a highly coordinated 'cross talk ' between mitochondrial and nuclear signals that can greatly influence cell behaviour. This review focuses upon the putative roles of altered mitochon drial physiology in the process of cellular transformation. Discussed are: mitochondria as targets of drug-induced cytotoxicity or cancer promotion, a s regulators of apoptosis, as sources of cell signalling through reactive o xygen species, and mitochondrial control of specific nuclear responses. (C) 2001 Elsevier Science B.V. All rights reserired.