Mitochondrial DNA in human malignancy.
Alterations in expression of mitochondrial DNA (mtDNA)-encoded polypeptides required for oxidative phosphorylation and cellular ATP generation may be a general characteristic of cancer cells. Mitochondrial DNA has been proposed to be involved in carcinogenesis because of high susceptibility to mutations and limited repair mechanisms in comparison to nuclear DNA. Since mtDNA lacks introns, it has been suggested that most mutations will occur in coding sequences and subsequent accumulation of mutations may lead to tumor formation. The mitochondrial genome is dependent upon the nuclear genome for transcription, translation, replication and repair, but precise mechanisms for how the two genomes interact and integrate with each other are poorly understood. In solid tumors, elevated expression of mtDNA-encoded subunits of the mitochondrial electron respiratory chain may reflect mitochondrial adaptation to perturbations in cellular energy requirements. In this paper, we review mitochondrial genomic aberrations reported in solid tumors of the breast, colon, stomach, liver, kidney, bladder, head/neck and lung as well as for hematologic diseases such as leukemia, myelodysplastic syndrome and lymphoma. We include data for elevated expression of mtDNA-encoded electron respiratory chain subunits in breast, colon and liver cancers and also the mutations reported in cancers of the colon, stomach, bladder, head/neck and lung. Finally, we examine the role of reactive oxygen species (ROS) generated by mitochondria in the process of carcinogenesis.
Penta
J S
JS
Office of Clinical Research, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, MD A2-05, Research Triangle Park, NC 27709, USA. penta@niehs.nih.gov
Johnson
F M
FM
Wachsman
J T
JT
Copeland
W C
WC
D001943:Breast Neoplasms / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D004579:Electron Transport / Q000235:genetics; D005260:Female; D019337:Hematologic Neoplasms / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics; D007938:Leukemia / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics; D008223:Lymphoma / Q000235:genetics; D008297:Male; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics
D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species