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Mitochondrial DNA in human malignancy.
J S Penta1, F M Johnson, J T Wachsman
1Office 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
Mutation Research
|May 10, 2001
Summary
Cancer cells often show altered mitochondrial DNA (mtDNA) expression, impacting energy production. Mutations and expression changes in mtDNA are implicated in tumor formation and progression across various cancers.
Area of Science:
- Mitochondrial biology
- Cancer genomics
- Cellular metabolism
Background:
- Mitochondrial DNA (mtDNA) alterations are increasingly recognized in cancer.
- mtDNA's susceptibility to mutations and limited repair suggest a role in carcinogenesis.
- The interplay between nuclear and mitochondrial genomes in cancer remains poorly understood.
Purpose of the Study:
- To review mitochondrial genomic aberrations in various solid tumors and hematologic malignancies.
- To examine the expression of mtDNA-encoded subunits in cancer.
- To explore the role of mitochondrial reactive oxygen species (ROS) in carcinogenesis.
Main Methods:
- Literature review of mitochondrial genomic aberrations in solid tumors (breast, colon, stomach, liver, kidney, bladder, head/neck, lung) and hematologic diseases.
- Analysis of reported data on elevated expression of mtDNA-encoded electron respiratory chain subunits.
- Inclusion of data on mtDNA mutations in various cancers.
Main Results:
- Alterations in mtDNA-encoded polypeptides are common in cancer cells, affecting oxidative phosphorylation and ATP generation.
- Elevated expression of mtDNA-encoded electron respiratory chain subunits is observed in breast, colon, and liver cancers.
- mtDNA mutations are reported in colon, stomach, bladder, head/neck, and lung cancers.
Conclusions:
- Mitochondrial genomic aberrations, including mutations and altered expression, are prevalent in diverse cancers.
- These alterations likely contribute to cancer development and progression by affecting cellular energy metabolism.
- Mitochondria-derived reactive oxygen species (ROS) may play a significant role in the carcinogenic process.