Somatic alterations in mitochondrial DNA produce changes in cell growth and metabolism supporting a tumorigenic phenotype

Jana Jandova, Mingjian Shi, Kimberly G. Norman, George P. Stricklin, James E. Sligh

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

There have been many reports of mitochondrial DNA (mtDNA) mutations associated with human malignancies. We have observed allelic instability in UV-induced cutaneous tumors at the mt-Tr locus encoding the mitochondrial tRNA for arginine. We examined the effects of somatic alterations at this locus by modeling the change in a uniform nuclear background by generating cybrids harboring allelic variation at mt-Tr. We utilized the naturally occurring mtDNA variation at mt-Tr within the BALB/cJ (BALB) and C57BL/6J (B6) strains of Mus musculus to transfer their mitochondria into a mouse ρ 0 cell line that lacked its own mtDNA. The BALB haplotype containing the mt-Tr 9821insA allele produced significant changes in cellular respiration (resulting in lowered ATP production), but increased rates of cellular proliferation in cybrid cells. Furthermore, the mtDNA genotype associated with UV-induced tumors endowed the cybrid cells with a phenotype of resistance to UV-induced apoptosis and enhanced migration and invasion capabilities. These studies support a role for mtDNA changes in cancer.

Original languageEnglish (US)
Pages (from-to)293-300
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1822
Issue number2
DOIs
StatePublished - Feb 1 2012

Keywords

  • Antioxidants
  • Migration and invasion
  • MtDNA mutation
  • Proliferation
  • Reactive oxygen species
  • UV-induced apoptosis

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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