A novel role of UBQLNs (ubiquilins) in regulating autophagy, MTOR signaling and v-ATPase function

UBQLNs (ubiquilins) are highly conserved proteins across species, characterized by interactions with proteasomes and ubiquitinated proteins via UBA and UBL domains, respectively. The role of UBQLNs as chaperone proteins of the ubiquitin-proteasome system (UPS) is well-defined; however, the connections between UBQLNs and autophagy remain unclear. A recent study published in Nature Cell Biology from Dr. Hugo J. Bellen's lab showed a novel role of UBQLNs in macroautophagy/autophagy regulation through v-ATPase-MTOR signaling using Drosophila and mammalian neuronal cells. Notably, the highlighted article also investigated the autophagy phenotype of a common amyotrophic lateral sclerosis (ALS)-associated mutation in the gene encoding UBQLN2, demonstrating the contribution of abnormal v-ATPase-MTOR-mediated autophagy in ALS pathogenesis.