A mammalian-specific Alex3/Gα q protein complex regulates mitochondrial trafficking, dendritic complexity, and neuronal survival
细胞生物学
线粒体
生物
作者
Ismael Izquierdo-Villalba,Serena Mirra,Yasmina Manso,Antoni Parcerisas,J. Rubio,Jaume Del Valle,Francisco J. Gil-Bea,Fausto Ulloa,Marina Herrero-Lorenzo,Ester Verdaguer,Cristiane Benincá,Rubén Darío Castro-Torres,Elena Rebollo,Gemma Marfany,Carme Auladell,Xavier Navarro,José Antonio Enríquez,Adolfo López de Munaín,Eduardo Soriano,Anna M. Aragay
出处
期刊:Science Signaling [American Association for the Advancement of Science (AAAS)] 日期:2024-02-06卷期号:17 (822)
标识
DOI:10.1126/scisignal.abq1007
摘要
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 Gα q inhibited mitochondrial trafficking in neurons through a mechanism that was independent of the canonical downstream PLCβ pathway. Mitoproteome analysis revealed that Gα q 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 Gα q 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/Gα q mitochondrial complex, which enables control of mitochondrial trafficking and neuronal death by GPCRs.