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


RESULTS
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
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.
Liesa
Marc
M
Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain.
Borda-d'Agua
Bárbara
B
Medina-Gómez
Gema
G
Lelliott
Christopher J
CJ
Paz
José Carlos
JC
Rojo
Manuel
M
Palacín
Manuel
M
Vidal-Puig
Antonio
A
Zorzano
Antonio
A
D000818:Animals; D002459:Cell Fusion; D002478:Cells, Cultured; D020558:GTP Phosphohydrolases / Q000235:genetics; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000502:physiology*; D053142:Mitochondrial Size / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011960:Receptors, Estrogen / Q000378:metabolism / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors; D014158:Transcription, Genetic; D000097983:ERRalpha Estrogen-Related Receptor
D020558:GTP Phosphohydrolases; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011960:Receptors, Estrogen; D015534:Trans-Activators; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor; C485290:Ppargc1a protein, mouse; C488751:Mfn2 protein, mouse