A new non-canonical pathway of Gαq protein regulating mitochondrial dynamics and bioenergetics

Contrary to previous assumptions, G proteins do not permanently reside on the plasma membrane, but are constantly monitoring the cytoplasmic surfaces of the plasma membrane and endomembranes. Here, we report that the G alpha(q) and G alpha(11) proteins locate at the mitochondria and play a role in a complex signaling pathway that regulates mitochondrial dynamics. Our results provide evidence for the presence of the heteromeric G protein (G alpha(q/11)beta gamma) at the outer mitochondrial membrane and for Ga at the inner membrane. Both localizations are necessary to maintain the proper equilibrium between fusion and fission; which is achieved by altering the activity of mitofusin proteins, Drpl, OPA1 and the membrane potential at both the outer and inner mitochondrial membranes. As a result of the absence of G alpha(q/11), there is a decrease in mitochondrial fusion rates and a decrease in overall respiratory capacity, ATP production and OXPHOS-dependent growth. These findings demonstrate that the presence of G alpha(q) proteins at the mitochondria serves as a physiological function: stabilizing elongated mitochondria and regulating energy production in Drpl and Opal dependent mechanisms. This thereby links organelle dynamics and physiology. (c) 2014 Elsevier Inc All rights reserved.