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Curr Biol. 2014 Mar 17;24(6):598-608. doi: 10.1016/j.cub.2014.01.071. Epub 2014 Mar 6.

Identification of transcriptional and metabolic programs related to mammalian cell size.

Author information

1
Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
2
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 61 Biopolis Drive, Proteos #03-09, Singapore 138673, Singapore; Department of Biochemistry, National University of Singapore, Singapore 117597, Singapore.
3
Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule Zürich, Wolfgang-Pauli Strasse 16, 8093 Zürich, Switzerland.
4
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 61 Biopolis Drive, Proteos #03-09, Singapore 138673, Singapore.
5
Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK. Electronic address: m.bjorklund@dundee.ac.uk.

Abstract

BACKGROUND:

Regulation of cell size requires coordination of growth and proliferation. Conditional loss of cyclin-dependent kinase 1 in mice permits hepatocyte growth without cell division, allowing us to study cell size in vivo using transcriptomics and metabolomics.

RESULTS:

Larger cells displayed increased expression of cytoskeletal genes but unexpectedly repressed expression of many genes involved in mitochondrial functions. This effect appears to be cell autonomous because cultured Drosophila cells induced to increase cell size displayed a similar gene-expression pattern. Larger hepatocytes also displayed a reduction in the expression of lipogenic transcription factors, especially sterol-regulatory element binding proteins. Inhibition of mitochondrial functions and lipid biosynthesis, which is dependent on mitochondrial metabolism, increased the cell size with reciprocal effects on cell proliferation in several cell lines.

CONCLUSIONS:

We uncover that large cell-size increase is accompanied by downregulation of mitochondrial gene expression, similar to that observed in diabetic individuals. Mitochondrial metabolism and lipid synthesis are used to couple cell size and cell proliferation. This regulatory mechanism may provide a possible mechanism for sensing metazoan cell size.

Comment in

PMID:
24613310
PMCID:
PMC3991852
DOI:
10.1016/j.cub.2014.01.071
[Indexed for MEDLINE]
Free PMC Article

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