Mitochondria: first line defense in sensing DNA stress

  • The number of mitochondria varies from 100 to 1000s in various cells & are packed with small circular DNA called mitochondrial DNA or mtDNA that is inherited from the mother to the progeny.
  • Researchers found new molecular pathways in the nucleus to counteract the DNA damage that is activated by interferon-stimulated genes (ISGs) when the mtDNA is damaged.
  • Factors that cause damage to nuclear DNA also cause the damage and release of mtDNA into the interior of the cells which in turn sets off molecular alarm bells by activating ISGs to protect nuclear DNA from damage.
  • Many copies of mitochondrial DNA in each cell contain only a few of its own DNA repair pathways makes it a very effective sensor of DNA stress quite before the nuclear DNA starts to get damaged.
  • Studies also found that doxorubicin-induced mitochondrial stress in melanoma became more resistant to doxorubicin Due to higher levels of the ISGs that were protecting the cell’s DNA.

Do you want to read more about this topic?

  1. Wu, Z., et al. (2019) Mitochondrial DNA stress signalling protects the nuclear genome. Nature Metabolism. doi.org/10.1038/s42255-019-0150-8.

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