Study of the role of the Gq protein in mitophagy

Abstract

Mitophagy is the mechanism developed by cells to degrade dysfunctional mitochondria. Alterations of this process have been found in several diseases such as cancer and Alzheimer’s disease. Therefore, it is fundamental to study the proteins with a role in mitophagy. So far, proteins that intervene in the biosynthesis of the autophagosome that will engulf defective mitochondria, such as TBC1D15, and others, as RILP, in the transport of the vesicle to the lysosome for degradation, have been described. Gq is a heterotrimeric G protein known to regulate the physiology of mitochondria, though its function in mitophagy is not well-known. The aim of the present work has been to analyze if Gq may inhibit this process by altering the location of the proteins TBC1D15, TBC1D17 and RILP. Also, it has been compared the effect of wild-type Gq and a constitutively active mutant, Gq(R183C). Herein, transfection of HEK293 cells followed by staining of mitophagy proteins was used to analyze the effect of Gq on their location. The results presented here are useful to propose a model of how inactive Gq may be displaced from mitochondria by TBC1D15/17 upon induction of mitophagy. In contrast, its activation impedes this displacement and as a consequence TBC1D15 is sent to the periphery, thus impairing this process.