2026-04-21T08:28:34Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/203632024-09-27T09:29:15Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
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
funder
Ministerio de Ciencia e Innovación (España)
funder
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
funder
Fundación ProCNIC
2024-07-09T13:19:26Z
2024-07-09T13:19:26Z
2024-02-06
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
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.
eng
A mammalian-specific Alex3/Gαq protein complex regulates mitochondrial trafficking, dendritic complexity, and neuronal survival.
journal article
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URL
https://repisalud.isciii.es/bitstreams/456cf532-d180-4f50-b307-3b7988035753/download
File
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application/pdf
A mammalian_specific Alex3_Sci Signal_2024.pdf
URL
https://repisalud.isciii.es/bitstreams/75c1dd0b-9e73-4ba3-80d7-4cb6e43e6a20/download
File
MD5
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text/plain
A mammalian_specific Alex3_Sci Signal_2024.pdf.txt