Mitochondrial Fusion Is Increased by the Nuclear Coactivator PGC-1ß
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 mi...
| Autores: | , , , , , , , , |
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| Tipo de documento: | artigo |
| Data de publicação: | 2008 |
| País: | España |
| Recursos: | Universidad Rey Juan Carlos |
| Repositório: | BURJC-Digital. Repositorio Institucional de la Universidad Rey Juan Carlos |
| OAI Identifier: | oai:burjcdigital.urjc.es:10115/3352 |
| Acesso em linha: | http://hdl.handle.net/10115/3352 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Biología y Biomedicina 3209.90 Farmacología Experimental |
| Resumo: | 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. |
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