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Inter-genomic cross talk between mitochondria and the nucleus plays an important role in tumorigenesis.

Publication ,  Journal Article
Singh, KK; Kulawiec, M; Still, I; Desouki, MM; Geradts, J; Matsui, S-I
Published in: Gene
July 18, 2005

Mitochondrial dysfunction is a hallmark of cancer cells. Consistent with this phenotype mutations in mitochondrial genome have been reported in all cancers examined to date. However, it is not clear whether mitochondrial genomic status in human cells affects nuclear genome stability and whether proteins involved in inter-genomic cross talk are involved in tumorigenesis. Using cell culture model and cybrid cell technology, we provide evidence that mitochondrial genetic status impacts nuclear genome stability in human cells. In particular our studies demonstrate 1) that depletion of mitochondrial genome (rho0) leads to chromosomal instability (CIN) reported to be present in variety of human tumors and 2) rho0 cells show transformed phenotype. Our study also demonstrates that mitochondrial genetic status plays a key role in regulation of a multifunctional protein APE1 (also known as Ref1 or HAP1) involved in transcription and DNA repair in the nucleus and the mitochondria. Interestingly we found that altered expression of APE1 in rho0 cells and tumorigenic phenotype can be reversed by exogenous transfer of wild type mitochondria in rho0 cells. Furthermore, we demonstrate that APE1 expression is altered in variety of primary tumors. Taken together, these studies suggest that inter-genomic cross talk between mitochondria and the nucleus plays an important role in tumorigenesis and that APE1 mediates this process.

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Published In

Gene

DOI

ISSN

0378-1119

Publication Date

July 18, 2005

Volume

354

Start / End Page

140 / 146

Location

Netherlands

Related Subject Headings

  • Translocation, Genetic
  • Tissue Array Analysis
  • Spectral Karyotyping
  • Signal Transduction
  • Neoplasms
  • Male
  • Immunohistochemistry
  • Hybrid Cells
  • Humans
  • Female
 

Citation

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Chicago
ICMJE
MLA
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Singh, K. K., Kulawiec, M., Still, I., Desouki, M. M., Geradts, J., & Matsui, S.-I. (2005). Inter-genomic cross talk between mitochondria and the nucleus plays an important role in tumorigenesis. Gene, 354, 140–146. https://doi.org/10.1016/j.gene.2005.03.027
Singh, Keshav K., Mariola Kulawiec, Ivan Still, Mohamed M. Desouki, Joseph Geradts, and Sei-Ichi Matsui. “Inter-genomic cross talk between mitochondria and the nucleus plays an important role in tumorigenesis.Gene 354 (July 18, 2005): 140–46. https://doi.org/10.1016/j.gene.2005.03.027.
Singh KK, Kulawiec M, Still I, Desouki MM, Geradts J, Matsui S-I. Inter-genomic cross talk between mitochondria and the nucleus plays an important role in tumorigenesis. Gene. 2005 Jul 18;354:140–6.
Singh, Keshav K., et al. “Inter-genomic cross talk between mitochondria and the nucleus plays an important role in tumorigenesis.Gene, vol. 354, July 2005, pp. 140–46. Pubmed, doi:10.1016/j.gene.2005.03.027.
Singh KK, Kulawiec M, Still I, Desouki MM, Geradts J, Matsui S-I. Inter-genomic cross talk between mitochondria and the nucleus plays an important role in tumorigenesis. Gene. 2005 Jul 18;354:140–146.
Journal cover image

Published In

Gene

DOI

ISSN

0378-1119

Publication Date

July 18, 2005

Volume

354

Start / End Page

140 / 146

Location

Netherlands

Related Subject Headings

  • Translocation, Genetic
  • Tissue Array Analysis
  • Spectral Karyotyping
  • Signal Transduction
  • Neoplasms
  • Male
  • Immunohistochemistry
  • Hybrid Cells
  • Humans
  • Female