Liesa, MarcBorda-d'Água, BárbaraMedina-Gómez, GemaLelliott, Christopher J.Paz, José CarlosRojo-Álvarez, José LuisPalacín, ManuelVidal-Puig, AntonioZorzano, Antonio2010-02-222010-02-222008-10-31Liesa M et al. (2008) Mitochondrial Fusion Is Increased by the Nuclear Coactivator PGC-1b. PLoS One. 2008;3(10):e3613. Epub 2008 Oct 31.PMID- 18974884http://hdl.handle.net/10115/3352There 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.enBiología y Biomedicinainfo:eu-repo/semantics/article10.1371/journal.pone.0003613info:eu-repo/semantics/openAccess3209.90 Farmacología Experimental