Cyclin B1/Cdk1 coordinates mitochondrial respiration for cell-cycle G2/M progression

Dev Cell. 2014 Apr 28;29(2):217-32. doi: 10.1016/j.devcel.2014.03.012.

Zhaoqing Wang ¹, Ming Fan ¹, Demet Candas ¹, Tie-Qiao Zhang ², Lili Qin ¹, Angela Eldridge ³, Sebastian Wachsmann-Hogiu ², Kazi M Ahmed ⁴, Brett A Chromy ³, Danupon Nantajit ¹, Nadire Duru ¹, Fuchu He ⁵, Min Chen ⁶, Toren Finkel ⁷, Lee S Weinstein ⁶, Jian Jian Li ⁸

Affiliations

1 Department of Radiation Oncology, University of California, Davis, Sacramento, CA 95817, USA.
2 Center for Biophotonics Science and Technology, University of California, Davis, Sacramento, CA 95817, USA.
3 Department of Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA 95817, USA.
4 Life Sciences Division, Department of Cancer and DNA Damage Response, Lawrence Berkeley National Laboratory, University of California, Berkeley, Berkeley, CA 94720, USA.
5 State Key Laboratory of Proteomics, Beijing Proteomics Research Center, Beijing 102206, China.
6 Signal Transduction Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
7 Center for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
8 Department of Radiation Oncology, University of California, Davis, Sacramento, CA 95817, USA; NCI-Designated Comprehensive Cancer Center, University of California Davis School of Medicine, Sacramento, CA 95817, USA. Electronic address: jijli@ucdavis.edu.

PMID: 24746669 DOI: 10.1016/j.devcel.2014.03.012

Abstract

A substantial amount of mitochondrial energy is required for cell-cycle progression. The mechanisms underlying the coordination of the mitochondrial respiration with cell-cycle progression, especially the G2/M transition, remain to be elucidated. Here, we show that a fraction of cyclin B1/CDK1 proteins localizes to the matrix of mitochondria and phosphorylates a cluster of mitochondrial proteins, including the complex I (CI) subunits in the respiratory chain. Cyclin B1/Cdk1-mediated CI phosphorylation enhances CI activity, whereas deficiency of such phosphorylation in each of the relevant CI subunits results in impairment of CI function. Mitochondria-targeted cyclin B1/CDK1 increases mitochondrial respiration with enhanced oxygen consumption and ATP generation, which provides cells with efficient bioenergy for G2/M transition and shortens overall cell-cycle time. Thus, cyclin B1/Cdk1-mediated phosphorylation of mitochondrial substrates allows cells to sense and respond to increased energy demand for G2/M transition and, subsequently, to upregulate mitochondrial respiration for successful cell-cycle progression.

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