Journal
CANCER BIOLOGY & THERAPY
Volume 7, Issue 8, Pages 1182-1190Publisher
LANDES BIOSCIENCE
DOI: 10.4161/cbt.7.8.6215
Keywords
mitochondria; epigenetic; retrograde; mitochondrial DNA; mtDNA depletion; RLGS; OXPHOS; rho(0)
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Funding
- NIH [RO1 121904, RO1CA116430]
- NY State Department of Health-Breast Cancer Program [CO21336]
- National Cancer Institute [CA 16056]
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Epigenetic modification in the nuclear genome plays a key role in human tumorigenesis. In this paper, we investigated whether changes in the mtDNA copy number frequently reported to vary in a number of human tumors induce methylation changes in the nucleus. We utilized the Restriction Landmark Genomic Scanning (RLGS) to identify genes that undergo changes in their methylation status in response to the depletion and repletion of mtDNA. Our study demonstrates that depletion of mtDNA results in significant changes in methylation pattern of a number of genes. Furthermore, our study suggests that methylation changes are reversed by the restoration of mtDNA in cells otherwise lacking the entire mitochondrial genome. These studies provide the first direct evidence that mitochondria regulate epigenetic modification in the nucleus that may contribute to tumorigenesis.
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