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oai:repisalud.isciii.es:20.500.12105/203632024-09-27T09:29:15Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Izquierdo-Villalba, Ismael author Mirra, Serena author Manso, Yasmina author Parcerisas, Antoni author Rubio, Javier author Del Valle, Jaume author Gil-Bea, Francisco J author Ulloa, Fausto author Herrero-Lorenzo, Marina author Verdaguer, Ester author Benincá, Cristiane author Castro-Torres, Rubén D author Rebollo, Elena author Marfany, Gemma author Auladell, Carme author Navarro, Xavier author Enriquez, Jose Antonio author López de Munain, Adolfo author Soriano, Eduardo author Aragay, Anna M author 2024-02-06 Mitochondrial dynamics and trafficking are essential to provide the energy required for neurotransmission and neural activity. We investigated how G protein-coupled receptors (GPCRs) and G proteins control mitochondrial dynamics and trafficking. The activation of Gαq inhibited mitochondrial trafficking in neurons through a mechanism that was independent of the canonical downstream PLCβ pathway. Mitoproteome analysis revealed that Gαq interacted with the Eutherian-specific mitochondrial protein armadillo repeat-containing X-linked protein 3 (Alex3) and the Miro1/Trak2 complex, which acts as an adaptor for motor proteins involved in mitochondrial trafficking along dendrites and axons. By generating a CNS-specific Alex3 knockout mouse line, we demonstrated that Alex3 was required for the effects of Gαq on mitochondrial trafficking and dendritic growth in neurons. Alex3-deficient mice had altered amounts of ER stress response proteins, increased neuronal death, motor neuron loss, and severe motor deficits. These data revealed a mammalian-specific Alex3/Gαq mitochondrial complex, which enables control of mitochondrial trafficking and neuronal death by GPCRs. Sci Signal. 2024 Feb 6;17(822):eabq1007. http://hdl.handle.net/20.500.12105/20363 38320000 10.1126/scisignal.abq1007 1937-9145 Science signaling A mammalian-specific Alex3/Gαq protein complex regulates mitochondrial trafficking, dendritic complexity, and neuronal survival.