The brain, a notoriously energy-hungry organ, consumes 20 to 25 percent of the body’s total energy. The high energy demand to sustain neuronal activities is met by the efficient transport and appropriate distribution of mitochondria, known as the cell’s powerhouses, within each neuron.
A recent study, published in Science Signaling, presented the pioneering discovery of a molecular complex responsible for the movement of mitochondria in neurons and the prevention of cell death. This complex, found exclusively in advanced mammals, opens new fronts for the development of treatments against neurodegenerative diseases such as Parkinson’s, neuromuscular disorders and certain types of cancer.
The project was conducted under the leadership of Professor Eduardo Soriano, from the University of Barcelona and the UB Neurosciences Institute (UBneuro), together with the Center for Biomedical Research Network on Neurodegenerative Diseases (CIBERNED), and researcher Anna María Aragay, from the Spanish National Research Council (CSIC) and the Barcelona Institute of Molecular Biology (IBMB-CSIC).
The research was collaborated by a diverse group of experts, including Ismael Izquierdo-Villalba (IBMB-CSIC), Serena Mirra and Yasmina Manso (UB-CIBERNED), as well as Adolfo López de Munain, from the Donostia University Hospital, Xavier Navarro , from the Autonomous University of Barcelona (UAB), both members of CIBERNED, and José Antonio Enríquez, from the National Center for Cardiovascular Research Carlos III (CNIC).
Essential energy for neuronal functioning In neurons, the presence of mitochondria along axons and dendrites is crucial for providing the energy necessary for neurotransmission and other energy-intensive cellular functions. “The meticulous distribution of mitochondria is vital for neuronal performance,” explains Professor Eduardo Soriano, one of the study leaders.
The research revealed that the Alex3/Gαq mitochondrial complex plays a key role in the distribution and movement of mitochondria throughout neurons, a process mediated by the interaction of the Gq protein with Alex3, a mitochondrial protein.
“The identification of the Alex3/Gαq complex as essential not only for mitochondrial transport, but also for neuronal health, marks a significant advance,” says Aragay. Inactivation of this system results in motor disorders and cell death, as observed in experimental models.
Furthermore, the researchers explored how the complex interacts with G protein-coupled receptors (GPCR), which are activated by a variety of molecules, influencing mitochondrial distribution and function and, consequently, neuronal growth and survival.
Future therapeutic perspectives The research highlights the potential for intervention in human diseases through the control of mitochondrial function, using GPCR receptors. This approach may be particularly promising for treating conditions characterized by mitochondrial dysfunction or for cancer therapies that aim to inhibit cellular metabolism.
“This discovery not only provides a deeper understanding of the cellular mechanisms underlying neuronal health, but also indicates promising avenues for developing new therapeutic strategies,” concludes the research team.
Reference: Izquierdo-Villalba, I., et al. (2024). A mammalian-specific Alex3/Gαq protein complex regulates mitochondrial trafficking, dendritic complexity, and neuronal survival. Science Signaling. doi:10.1126/scisignal.abq1007 .
