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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
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.
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It is part of: Cell Metabolism, 2021, vol. 33, num. 9, p. 1820-1835
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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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