The Biological Function Of Rab GTPase Family In Mitophagy

In eukrayotic cells,selective autophagy removes damaged organelles,misfolded protein aggregates or invading pathogens to maintain the cellular homeostasis.Unlike bulk autophagy,selective autophagy requires cargo receptors to ensure specific recognition,isolation and engulfment of designated substrates for subsequent lysosomal degradation.However,it remains poorly understood that how the targeted biosynthesis of autophagosomes in selective autophagy is spatiotemporally regulated.Based on our previous studies,we hypothesized that Rab GTPases are involved in the regulation of autophagosome biogenesis by interacting with cargo receptors.Rab GTPases are widely distributed in the intracellular membrane-bound organelles and play important roles in vesicle transport and fusion.We found that majority of human Rab GTPase family members were subjected to autophagic degradation in a manner similar to LC3-II and cargo receptors.Further studies indicated that these Rab GTPases broadly interact with cargo receptors.In a proof-of-concept study,we found that during mitophagy,Rab GTPases were recruited to depolarized mitochondria,and endogenous Rab GTPases showed autophagic degradation.Importantly,overexpression of Rab GTPases promoted mitophagy,while the absence of Rab GTPases inhibited mitophagy.Mechanistically,Rab GTPases coordinated with mitophagy receptors to regulate mitophagy.In conclusion,our data suggests a general mechanism in mitophagy initiation.