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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/180330
Mitochondrial cristae-remodeling protein OPA1 in POMC neurons couples Ca2+ homeostasis with adipose tissue lipolysis
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Appropriate cristae remodeling is a determinant of mitochondrial function and bioenergetics and thus represents a crucial process for cellular metabolic adaptations. Here, we show that mitochondrial cristae architecture and expression of the master cristae-remodeling protein OPA1 in proopiomelanocortin (POMC) neurons, which are key metabolic sensors implicated in energy balance control, is affected by fluctuations in nutrient availability. Genetic inactivation of OPA1 in POMC neurons causes dramatic alterations in cristae topology, mitochondrial Ca2+ handling, reduction in alpha-melanocyte stimulating hormone (α-MSH) in target areas, hyperphagia, and attenuated white adipose tissue (WAT) lipolysis resulting in obesity. Pharmacological blockade of mitochondrial Ca2+ influx restores α-MSH and the lipolytic program, while improving the metabolic defects of mutant mice. Chemogenetic manipulation of POMC neurons confirms a role in lipolysis control. Our results unveil a novel axis that connects OPA1 in POMC neurons with mitochondrial cristae, Ca2+ homeostasis, and WAT lipolysis in the regulation of energy balance.
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GÓMEZ VALADÉS, Alicia g., POZO, Macarena, VARELA, Luis, BOUDJADJA, Mehdi boutagouga, RAMÍREZ, Sara, CHIVITE, Iñigo, EYRE, Elena, HADDAD TOVOLLI, Roberta, OBRI, Arnaud, MILÀ GUASCH, Maria, ALTIRRIBA GUTIÉRREZ, Jordi, SCHNEEBERGER, Marc, IMBERNÓN, Mónica, GARCIA RENDUELES, Angela r., GAMA-PEREZ, Pau, ROJO RUIZ, Jonathan, RÁCZ, Bence, ALONSO, Maria teresa, GOMIS, Ramon, ZORZANO OLARTE, Antonio, D’AGOSTINO, Giuseppe, ALVAREZ, Clara v., NOGUEIRAS, Rubén, GARCIA ROVES, Pablo m., HORVATH, Tamas l., CLARET I CARLES, Marc. Mitochondrial cristae-remodeling protein OPA1 in POMC neurons couples Ca2+ homeostasis with adipose tissue lipolysis. _Cell Metabolism_. 2021. Vol. 33, núm. 9, pàgs. 1820-1835. [consulta: 23 de gener de 2026]. ISSN: 1932-7420. [Disponible a: https://hdl.handle.net/2445/180330]