A new non-canonical pathway of Gα(q) protein regulating mitochondrial dynamics and bioenergetics

Cell Signal. 2014 May;26(5):1135-46. doi: 10.1016/j.cellsig.2014.01.009. Epub 2014 Jan 18.


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 Gαq and Gα11 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 (Gαq/11βγ) at the outer mitochondrial membrane and for Gαq 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, Drp1, OPA1 and the membrane potential at both the outer and inner mitochondrial membranes. As a result of the absence of Gαq/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 Gαq proteins at the mitochondria serves as a physiological function: stabilizing elongated mitochondria and regulating energy production in Drp1 and Opa1 dependent mechanisms. This thereby links organelle dynamics and physiology.

Keywords: Drp; Fission; Fusion; Gq; Heterotrimeric G proteins; Mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Dynamins / metabolism
  • Energy Metabolism*
  • GTP Phosphohydrolases / metabolism
  • GTP-Binding Protein alpha Subunits, Gq-G11 / antagonists & inhibitors
  • GTP-Binding Protein alpha Subunits, Gq-G11 / genetics
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism*
  • HEK293 Cells
  • Humans
  • Membrane Potential, Mitochondrial
  • Mice
  • Mice, Transgenic
  • Mitochondria / metabolism
  • Mitochondrial Dynamics
  • Mitochondrial Membranes / metabolism
  • NIH 3T3 Cells
  • Oxidative Phosphorylation
  • Protein Subunits / antagonists & inhibitors
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • RNA, Small Interfering / metabolism


  • Protein Subunits
  • RNA, Small Interfering
  • GTP Phosphohydrolases
  • Opa1 protein, mouse
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Dnm1l protein, mouse
  • Dynamins