title: Cyclin B1/Cdk1 coordinates mitochondrial respiration for cell-cycle G2/M progression.
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.
authors.affiliation: Department of Radiation Oncology, University of California, Davis, Sacramento, CA 95817, USA.
authors.forename: Zhaoqing
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, University of California, Davis, Sacramento, CA 95817, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
authors.affiliation: Department of Radiation Oncology, University of California, Davis, Sacramento, CA 95817, USA.
authors.forename: Demet
authors.initials: D
authors.lastname: Candas
authors.affiliation: Center for Biophotonics Science and Technology, University of California, Davis, Sacramento, CA 95817, USA.
authors.forename: Tie-Qiao
authors.initials: TQ
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, University of California, Davis, Sacramento, CA 95817, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA 95817, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Eldridge
authors.affiliation: Center for Biophotonics Science and Technology, University of California, Davis, Sacramento, CA 95817, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wachsmann-Hogiu
authors.affiliation: Life Sciences Division, Department of Cancer and DNA Damage Response, Lawrence Berkeley National Laboratory, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Kazi M
authors.initials: KM
authors.lastname: Ahmed
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA 95817, USA.
authors.forename: Brett A
authors.initials: BA
authors.lastname: Chromy
authors.affiliation: Department of Radiation Oncology, University of California, Davis, Sacramento, CA 95817, USA.
authors.forename: Danupon
authors.initials: D
authors.lastname: Nantajit
authors.affiliation: Department of Radiation Oncology, University of California, Davis, Sacramento, CA 95817, USA.
authors.forename: Nadire
authors.initials: N
authors.lastname: Duru
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteomics Research Center, Beijing 102206, China.
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.affiliation: Signal Transduction Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Center for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Toren
authors.initials: T
authors.lastname: Finkel
authors.affiliation: Signal Transduction Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Lee S
authors.initials: LS
authors.lastname: Weinstein
authors.affiliation: 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.
authors.forename: Jian Jian
authors.initials: JJ
authors.lastname: Li
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000502:physiology*; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D004579:Electron Transport / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology; D016195:G2 Phase / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D008099:Liver / Q000166:cytology; D061986:MCF-7 Cells; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000502:physiology; D010766:Phosphorylation / Q000502:physiology; D013379:Substrate Specificity / Q000502:physiology; D000095043:Cyclin-Dependent Kinase-Activating Kinase
chemical_list: C534699:CCNB1 protein, human; C534700:Ccnb1 protein, mouse; D056744:Cyclin B1; D024101:Mitochondrial Proteins; D016203:CDC2 Protein Kinase; D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase
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