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PMID:24746669

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Citation

Wang, Z, Fan, M, Candas, D, Zhang, TQ, Qin, L, Eldridge, A, Wachsmann-Hogiu, S, Ahmed, KM, Chromy, BA, Nantajit, D, Duru, N, He, F, Chen, M, Finkel, T, Weinstein, LS and Li, JJ (2014) Cyclin B1/Cdk1 coordinates mitochondrial respiration for cell-cycle G2/M progression. Dev. Cell 29:217-32

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.

Links

PubMed PMC4156313 Online version:10.1016/j.devcel.2014.03.012

Keywords

Animals; CDC2 Protein Kinase/genetics; CDC2 Protein Kinase/metabolism; Cell Division/physiology; Cyclin B1/genetics; Cyclin B1/metabolism; Cyclin-Dependent Kinases/genetics; Cyclin-Dependent Kinases/metabolism; Electron Transport/physiology; Epithelial Cells/cytology; G2 Phase/physiology; Humans; Keratinocytes/cytology; Liver/cytology; MCF-7 Cells; Mice; Mitochondria/metabolism; Mitochondrial Proteins/genetics; Mitochondrial Proteins/metabolism; Mitosis/physiology; Phosphorylation/physiology; Substrate Specificity/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:NDUS2

part_of

GO:0005747: mitochondrial respiratory chain complex I

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:NDUS2

involved_in

GO:0042775: mitochondrial ATP synthesis coupled electron transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NDUB6

part_of

GO:0005747: mitochondrial respiratory chain complex I

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:NDUB6

involved_in

GO:0042775: mitochondrial ATP synthesis coupled electron transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TOM40

located_in

GO:0005743: mitochondrial inner membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CH60

located_in

GO:0005759: mitochondrial matrix

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CDK1

colocalizes_with

GO:0005759: mitochondrial matrix

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CCNB1

enables

GO:0019901: protein kinase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P06493

F

Seeded From UniProt

complete

HUMAN:CCNB1

part_of

GO:0097125: cyclin B1-CDK1 complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CCNB1

colocalizes_with

GO:0005759: mitochondrial matrix

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CCNB1

involved_in

GO:0010971: positive regulation of G2/M transition of mitotic cell cycle

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CCNB1

enables

GO:0061575: cyclin-dependent protein serine/threonine kinase activator activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:CCNB1

involved_in

GO:1905448: positive regulation of mitochondrial ATP synthesis coupled electron transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CCNB1

colocalizes_with

GO:0005759: mitochondrial matrix

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:NDUV1

part_of

GO:0005747: mitochondrial respiratory chain complex I

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:NDUV1

involved_in

GO:0042775: mitochondrial ATP synthesis coupled electron transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NDUV3

part_of

GO:0005747: mitochondrial respiratory chain complex I

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:NDUV3

involved_in

GO:0042775: mitochondrial ATP synthesis coupled electron transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NDUAC

part_of

GO:0005747: mitochondrial respiratory chain complex I

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:NDUAC

involved_in

GO:0042775: mitochondrial ATP synthesis coupled electron transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TIM13

located_in

GO:0005743: mitochondrial inner membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CH60

part_of

GO:0005759: mitochondrial matrix

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CDK1

enables

GO:0030332: cyclin binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P14635

F

Seeded From UniProt

complete

HUMAN:CDK1

part_of

GO:0097125: cyclin B1-CDK1 complex

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CDK1

colocalizes_with

GO:0005759: mitochondrial matrix

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CDK1

involved_in

GO:0006468: protein phosphorylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CDK1

enables

GO:0004693: cyclin-dependent protein serine/threonine kinase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:CDK1

involved_in

GO:0010971: positive regulation of G2/M transition of mitotic cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CDK1

involved_in

GO:1905448: positive regulation of mitochondrial ATP synthesis coupled electron transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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