Examinando por Autor "Zorzano, Antonio"

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Mitochondrial Fusion Is Increased by the Nuclear Coactivator PGC-1ß
(PLoS ONE, 2008-10-31) Liesa, Marc; Borda-d'Água, Bárbara; Medina-Gómez, Gema; Lelliott, Christopher J.; Paz, José Carlos; Rojo-Álvarez, José Luis; Palacín, Manuel; Vidal-Puig, Antonio; Zorzano, Antonio
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.
SUCNR1 controls an anti-inflammatory program in macrophages to regulate the metabolic response to obesity
(Nature, 2019-05) Keiran, Noelia; Ceperuelo-Mallafré, Victoria; Calvo, Enrique; Hernández-Alvarez, María isabel; Ejarque, Miriam; Núñez-Roa, Catalina; Hormillo, Daniel; Maymó-Masip, Elsa; Rodriguez, M Mar; Fradera, Rosa; de la Rosa, Juan Vladimir; Jorba, Rosa; Megia, Ana; Zorzano, Antonio; Medina-Gomez, Gema; Serena, Carolina; Castrillo, Antonio; Vendrell, Joan; Fernández-Veledo, Sonia
Succinate is a signaling metabolite sensed extracellularly by succinate receptor 1 (SUNCR1). The accumulation of succinate in macrophages is known to activate a pro-inflammatory program; however, the contribution of SUCNR1 to macrophage phenotype and function has remained unclear. Here we found that activation of SUCNR1 had a critical role in the anti-inflammatory responses in macrophages. Myeloid-specific deficiency in SUCNR1 promoted a local pro-inflammatory phenotype, disrupted glucose homeostasis in mice fed a normal chow diet, exacerbated the metabolic consequences of diet-induced obesity and impaired adipose-tissue browning in response to cold exposure. Activation of SUCNR1 promoted an anti-inflammatory phenotype in macrophages and boosted the response of these cells to type 2 cytokines, including interleukin-4. Succinate decreased the expression of inflammatory markers in adipose tissue from lean human subjects but not that from obese subjects, who had lower expression of SUCNR1 in adipose-tissue-resident macrophages. Our findings highlight the importance of succinate-SUCNR1 signaling in determining macrophage polarization and assign a role to succinate in limiting inflammation.