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PLoS One. 2008;3(10):e3613. doi: 10.1371/journal.pone.0003613. Epub 2008 Oct 31.

Mitochondrial fusion is increased by the nuclear coactivator PGC-1beta.

Author information

1
Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain.

Abstract

BACKGROUND:

There is no evidence to date on whether transcriptional regulators are able to shift the balance between mitochondrial fusion and fission events through selective control of gene expression.

METHODOLOGY/PRINCIPAL FINDINGS:

Here, we demonstrate that reduced mitochondrial size observed in knock-out mice for the transcriptional regulator PGC-1beta is associated with a selective reduction in Mitofusin 2 (Mfn2) expression, a mitochondrial fusion protein. This decrease in Mfn2 is specific since expression of the remaining components of mitochondrial fusion and fission machinery were not affected. Furthermore, PGC-1beta increases mitochondrial fusion and elongates mitochondrial tubules. This PGC-1beta-induced elongation specifically requires Mfn2 as this process is absent in Mfn2-ablated cells. Finally, we show that PGC-1beta increases Mfn2 promoter activity and transcription by coactivating the nuclear receptor Estrogen Related Receptor alpha (ERRalpha).

CONCLUSIONS/SIGNIFICANCE:

Taken together, our data reveal a novel mechanism by which mammalian cells control mitochondrial fusion. In addition, we describe a novel role of PGC-1beta in mitochondrial physiology, namely the control of mitochondrial fusion mainly through Mfn2.

PMID:
18974884
PMCID:
PMC2570954
DOI:
10.1371/journal.pone.0003613
[Indexed for MEDLINE]
Free PMC Article
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