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Title: | Mitochondrial cristae-remodeling protein OPA1 in POMC neurons couples Ca2+ homeostasis with adipose tissue lipolysis |
Author: | 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 |
Keywords: | Hipotàlem Obesitat Hypothalamus Obesity |
Issue Date: | 1-Aug-2021 |
Publisher: | Elsevier BV |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.cmet.2021.07.008 |
It is part of: | Cell Metabolism, 2021, vol. 33, num. 9, p. 1820-1835 |
URI: | http://hdl.handle.net/2445/180330 |
Related resource: | https://doi.org/10.1016/j.cmet.2021.07.008 |
ISSN: | 1932-7420 |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Publicacions de projectes de recerca finançats per la UE |
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