| First Author | Izquierdo-Villalba I | Year | 2024 |
| Journal | Sci Signal | Volume | 17 |
| Issue | 822 | Pages | eabq1007 |
| PubMed ID | 38320000 | Mgi Jnum | J:345823 |
| Mgi Id | MGI:7611778 | Doi | 10.1126/scisignal.abq1007 |
| Citation | Izquierdo-Villalba I, et al. (2024) A mammalian-specific Alex3/Galpha(q) protein complex regulates mitochondrial trafficking, dendritic complexity, and neuronal survival. Sci Signal 17(822):eabq1007 |
| abstractText | 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 Galpha(q) inhibited mitochondrial trafficking in neurons through a mechanism that was independent of the canonical downstream PLCbeta pathway. Mitoproteome analysis revealed that Galpha(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 Galpha(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/Galpha(q) mitochondrial complex, which enables control of mitochondrial trafficking and neuronal death by GPCRs. |
