Why do we need G proteins in the mitochondria?

Anne Aragay, Institut de Biologia Molecular de Barcelona, Spain

06 mai 2024


Infos pratiques

14h00 -
Salle Méchain 1
Accès mobilité réduite

Invitée par Ralf Jockers

Anna M. Aragay is the head of the “Intracellular Signaling” group at the Institute for Molecular Biology-CSIC (IBMB-CSIC) in Barcelona (Spain). She obtained her PhD. at the Autonomous University of Barcelona (UAB) and she moved to the California Institute of Technology (Caltech) at USA for a postdoc with Prof. M. Simon where she focus her interest in signal transduction processes. In particular she studied signaling processes regulated by G protein from the Gq and G12 family in different signaling pathways. During this period, she had a close collaboration with Prof. H. Brown at UCSD where she implemented microinjecting techniques for signal inhibition and with Prof. H. Lester at Caltech using electrophysiology for GPCR studies. She joined the group of Prof. F. Mayor at Centro de Biologia Molecular Severo Ochoa in Madrid, as a junior scientist, studying chemokine signaling. She stablished her research group in the University of Bergen in Norway as Associate Professor and became Professor in 2005. In this period, she directed the Norwegian National platform for Molecular Imaging (MIC). In mid-2006, she moved to IBMB in Barcelona where she established her actual group. Her research has taken a major twist in the last years with the discovery of the direct control of mitochondria by G proteins.

About his research:

Our group demonstrated the localization of Gαq subunit at the mitochondria membrane that affects mitochondrial morphology and is required for OXPHOS function. Through a proteome-wide approach we identified mitochondrial partners for Gαq. This analysis identified a group of proteins involved in the process of mitophagy and others in control of the mitochondria motility, among others. Our results show that the mitochondrial trafficking protein, armadillo-domain protein (Alex3), directly interacts with Gq and acts as an activator independent of Gbg and GPCRs. Alex protein is a member of the Eutherian-specific Armcx gene family localized to the mitochondria. Alex3 is preferentially expressed in the upper layers of the developing cerebral cortex. Life-cell imaging of mitochondria in hippocampal neurons revealed that Gαq is needed for the regulation of the anterograde and retrograde movement of mitochondria along the axons. Utilizing knockout and knockdown techniques, we demonstrated that Alex3 is required for Gαq effects on mitochondrial trafficking and dendritic growth. These proteins control mitochondrial distribution and trafficking, dendritic complexity, synapse formation and neuronal survival. More recent work has shown that Gαq is also needed for the regulation of autophagy and mitophagy processes.

Some recent publications:

Izquierdo-Villaba I, Mirra S, Manso Y, Parcerisas A, Rubio J, Del Valle, et al..Soriano E, and Aragay AM*. A mammalian-specific Alex3/Gaq protein complex regulates mitochondrial trafficking, dendritic complexity, and neuronal survival.  Science Sig. (2024)

Hernandez-Perez I, Rubio J, Baumann A, Girao H, Ferrando M, Rebollo E, Aragay AM*, Geli* MI. Kazrin promotes dynein/dynactin dependent traffic from early to recycling endosomes. Elife. (2023) Apr 25;12:e83793.

Sofía C, Sanz-Flores M, Caballero A, Tasset I, Rebollo E, Diaz A, Aragay AM, Cuervo AM, Mayor F, and C. Ribas. Gq activation modulates autophagy by promoting mTORC1 signaling. (2021) Nature Communication 27;12(1):4540.

Selheim F, Aasebø E, Ribas C, Aragay* AM. An Overview on G Protein-coupled Receptor-induced Signal Transduction in Acute Myeloid Leukemia (2019) Curr Med Chem. 2019;26(28):5293-5316.

Pons M, Izquierdo I, Andreu-Carbó M, Garrido G, Planagumà J, Muriel O, Del Pozo MA, Geli MI, Aragay* AM. Phosphorylation of Filamin A regulates chemokine receptor CCR2B recycling. (2017) J Cell Sci. 130(2):490-501.