Liesa Torre-Marín, MontserratBorda d'Agua, BárbaraMedina Gómez, GemaLelliott, Christopher J.Paz, José CarlosRojo, ManuelPalacín Prieto, ManuelVidal-Puig, AntonioZorzano Olarte, Antonio2013-05-072013-05-072008-101932-6203https://hdl.handle.net/2445/43201Background 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-1β 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-1β increases mitochondrial fusion and elongates mitochondrial tubules. This PGC-1β-induced elongation specifically requires Mfn2 as this process is absent in Mfn2-ablated cells. Finally, we show that PGC-1β increases Mfn2 promoter activity and transcription by coactivating the nuclear receptor Estrogen Related Receptor α (ERRα). 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-1β in mitochondrial physiology, namely the control of mitochondrial fusion mainly through Mfn2.11 p.application/pdfengcc-by (c) Liesa, M. et al., 2008http://creativecommons.org/licenses/by/3.0/esMitocondrisRegulació genèticaMitochondriaGenetic regulationinfo:eu-repo/semantics/article5678472013-05-07info:eu-repo/semantics/openAccess18974884