Mitochondrial contributions to cancer cell physiology: potential for drug development.
Mitochondria make an integral contribution to the regulation of several aspects of cell biology such as energy production, molecular metabolism, redox status, calcium signalling 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 extracellular 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 mitochondrial physiology in the process of cellular transformation. Discussed are: mitochondria as targets of drug-induced cytotoxicity or cancer promotion, as regulators of apoptosis, as sources of cell signalling through reactive oxygen species, and mitochondrial control of specific nuclear responses.
Preston
T J
TJ
Department of Pathology and Molecular Medicine, McMaster University, 699 Concession St., Hamilton, Ontario, Canada L8V 5C2.
Abadi
A
A
Wilson
L
L
Singh
G
G
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002467:Cell Nucleus / Q000502:physiology; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009153:Mutagens / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism*
D000970:Antineoplastic Agents; D004272:DNA, Mitochondrial; D007473:Ion Channels; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009153:Mutagens; D017382:Reactive Oxygen Species; D014157:Transcription Factors