CDK1 Enhances Mitochondrial Bioenergetics for Radiation-Induced DNA Repair

Lili Qin, Ming Fan, Demet Candas, Guochun Jiang, Stelios Papadopoulos, Lin Tian, Gayle Woloschak, David J. Grdina, Jian-Jian Li

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Nuclear DNA repair capacity is a critical determinant of cell fate under genotoxic stress conditions. DNA repair is a well-defined energy-consuming process. However, it is unclear how DNA repair is fueled and whether mitochondrial energy production contributes to nuclear DNA repair. Here, we report a dynamic enhancement of oxygen consumption and mitochondrial ATP generation in irradiated normal cells, paralleled with increased mitochondrial relocation of the cell-cycle kinase CDK1 and nuclear DNA repair. The basal and radiation-induced mitochondrial ATP generation is reduced significantly in cells harboring CDK1 phosphorylation-deficient mutant complex I subunits. Similarly, mitochondrial ATP generation and nuclear DNA repair are also compromised severely in cells harboring mitochondrially targeted, kinase-deficient CDK1. These results demonstrate a mechanism governing the communication between mitochondria and the nucleus by which CDK1 boosts mitochondrial bioenergetics to meet the increased cellular fuel demand for DNA repair and cell survival under genotoxic stress conditions. Qin et al. identify communication between mitochondrial bioenergetics and nuclear DNA repair. Upon radiation, the mitotic kinase CDK1 relocates to mitochondria and activates mitochondrial complex I. The resulting ATP generation is required for efficient DNA repair.

Original languageEnglish (US)
JournalCell Reports
DOIs
StateAccepted/In press - Jun 18 2015

Keywords

  • CDK1
  • DNA repair
  • Mitochondrial bioenergetics
  • Radiation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Qin, L., Fan, M., Candas, D., Jiang, G., Papadopoulos, S., Tian, L., Woloschak, G., Grdina, D. J., & Li, J-J. (Accepted/In press). CDK1 Enhances Mitochondrial Bioenergetics for Radiation-Induced DNA Repair. Cell Reports. https://doi.org/10.1016/j.celrep.2015.11.015