Gomez-Valades 2021 Cell Metab

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Gómez-Valadés AG, Pozo M, Varela L, Boudjadja MB, Ramírez S, Chivite I, Eyre E, Haddad-Tóvolli R, Obri A, Milà-Guasch M, Altirriba J, Schneeberger M, Imbernón M, Garcia-Rendueles AR, Gama-Perez P, Rojo-Ruiz J, Rácz B, Alonso MT, Gomis R, Zorzano A, D'Agostino G, Alvarez CV, Nogueiras R, Garcia-Roves PM, Horvath TL, Claret M (2021) Mitochondrial cristae-remodeling protein OPA1 in POMC neurons couples Ca<sup>2+</sup> homeostasis with adipose tissue lipolysis . Cell Metab 33:1820-35.e9.

» PMID: 34343501 Open Access

Gomez-Valades Alicia G, Pozo Macarena, Varela Luis, Boutagouga Boudjadja Mehdi, Ramirez Sara, Chivite Inigo, Eyre Elena, Haddad-Tovolli Roberta, Obri Arnaud, Mila-Guasch Maria, Altirriba Jordi, Schneeberger Marc, Imbernon Moncia, Garcia-Rendueles Angela R, Gama-Perez Pau, Rojo-Ruiz Jonathan, Racz Bence, Alonso Maria Teresa, Gomis Ramon, Zorzano Antonio, D'Agostino Giuseppe, Alvarez Clara V, Nogueiras Ruben, Garcia-Roves Pablo M, Horvath Tamas L, Claret Marc (2021) Cell Metab

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. Keywords: OPA-1, POMC neurons, Cristae, Hypothalamus, Lipolysis, Mitochondria, Obesity Bioblast editor: Plangger M O2k-Network Lab: ES Barcelona Zorzano A, ES Barcelona Garcia-Roves PM, ES Barcelona Claret M


Labels: MiParea: Respiration, mt-Structure;fission;fusion, Exercise physiology;nutrition;life style 


Organism: Mouse  Tissue;cell: Nervous system  Preparation: Permeabilized tissue, Homogenate 


Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k 

2021-10