A mammalian-specific Alex3/Gαq protein complex regulates mitochondrial trafficking, dendritic complexity, and neuronal survival

A study led by AM Aragay (IBMB) and E. Soriano (UB and CIBERNED) reveals a novel mechanism that connects neuronal cell death with motor disfunctions specific to the most evolved mammals (Eutherians).

Abstract:

Mitochondrial dynamics and trafficking are essential to provide the energy required for neurotransmission and neural activity. This study reveals that mitochondrial traffic in neurons requires the interaction between two proteins: a signaling protein, Gα_q, and a mitochondrial protein, Alex3, specific to the most evolved mammals (Eutherians). The Alex3/Gα_q complex interacts with the mitochondrial machinery to distribute and transport these cellular organelles through the axons and dendrites of neurons. Deficits in this system, including mice with a specific CNS deficiency in Alex3, give rise to reduce mitochondrial traffic, dendritic and axonal arborization, and an increase in neuronal death that together produce motor and energy alterations. The study reveal that this mechanism allows the control of mitochondrial traffic and neuronal cell death by GPCR (G Protein Coupled Receptors). The new molecular complex could help to identify novel therapeutic targets against neurodegenerative diseases such as Parkinson’s, neuromuscular pathologies or even some types of tumors.

The study was a close collaboration between the groups of AM Aragay (IBMB), and E. Soriano (UB-CIBERNED), and with the participation of the groups of A. López de Munain, (Hospital Universitario de Donostia), X. Navarro (UAB) J. A. Enríquez (CNIC-CIBERFES).

Reference:

Izquierdo-Villalba,I, Mirra, S,, Manso, Y, Parcerisas,A,  Rubio, J, Del Valle, J, Gil-Bea, FJ, Ulloa, F, Herrero-Lorenzo^, M, Verdaguer, E, Benincá, C, Castro-Torres, RD, Rebollo^,, E, Marfany, G, Auladell, C, Navarro^, X, Enríquez, JA, López de Munain, L, Soriano^, E and AM Aragay. «A mammalian-specific Alex3/Gα_q protein complex regulates mitochondrial trafficking, dendritic complexity, and neuronal survival». Science Signaling, Feb 6 2024, 17, 822. Doi: 10.1126/scisignal.abq1007