Apoptosis induced by persistent single-strand breaks in mitochondrial genome: Critical role of EXOG (5′-exo/endonuclease) in their repair

Anne W. Tann, Istvan Boldogh, Gregor Meiss, Wei Qian, Bennett Van Houten, Sankar Mitra, Bartosz Szczesny

Research output: Contribution to journalArticle

99 Scopus citations


Reactive oxygen species (ROS), continuously generated as byproducts of respiration, inflict more damage on the mitochondrial (mt) than on the nuclear genome because of the nonchromatinized nature and proximity to the ROS source of the mitochondrial genome. Such damage, particularly single-strand breaks (SSBs) with 5′-blocking deoxyribose products generated directly or as repair intermediates for oxidized bases, is repaired via the base excision/SSB repair pathway in both nuclear and mt genomes. Here, we show that EXOG, a 5′-exo/endonuclease and unique to the mitochondria unlike FEN1 or DNA2, which, like EXOG, has been implicated in the removal of the 5′-blocking residue, is required for repairing endogenous SSBs in the mt genome. EXOG depletion induces persistent SSBs in the mtDNA, enhances ROS levels, and causes apoptosis in normal cells but not in mt genome-deficient rho0 cells. Thus, these data show for the first time that persistent SSBs in the mt genome alone could provide the initial trigger for apoptotic signaling in mammalian cells.

Original languageEnglish (US)
Pages (from-to)31975-31983
Number of pages9
JournalJournal of Biological Chemistry
Issue number37
StatePublished - Sep 16 2011


ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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