Abstract
ABSTRACTAutophagy is an essential physiological process that maintains cellular homeostasis by eliminating harmful protein aggregates, damaged organelles and certain pathogens through lysosomal degradation. During autophagy specialized structures, known as autophagosomes are formed that recruit the cargo through autophagy receptors, and deliver it to lysosomes. Optineurin (Optn) is an autophagy receptor that mediates cargo selective autophagy. Recently, we have identified a novel function of Optn that promotes autophagosome formation during non-selective autophagy. Optn-deficient cells show reduced formation of autophagosomal protein LC3-II and lower number of autophagosomes as well as autolysosomes. Interestingly, formation of phagophores is increased in Optn-deficient cells. This suggests that Optn promotes autophagosome formation by potentiating LC3-II production and phagophore maturation. Phosphorylation of Optn at Ser-177 is required for promoting autophagosome formation. Here, we discuss various aspects of the role of Optn in the formation of autophagosomes and Atg16L1-positive vesicles. We also discuss the potential role of Rab1a-Optn interaction.
Highlights
Autophagy is an essential physiological process that maintains cellular homeostasis by eliminating harmful protein aggregates, damaged organelles and certain pathogens through lysosomal degradation
We reported a novel function of Optn in phagophore maturation that promotes LC3-II production and autophagosome formation during basal and starvation induced autophagy, which are considered as non-selective autophagy [8]
Formation of LC3-II occurs by conjugation of LC3-I with the lipid phosphatidyethanolamine through a ubiquitination-like reaction, which is mediated by a complex of autophagy-related proteins, the Atg12-5-16L1 complex [9]
Summary
Autophagy is an essential physiological process that maintains cellular homeostasis by eliminating harmful protein aggregates, damaged organelles and certain pathogens through lysosomal degradation. KEYWORDS Autophagy; optineurin; phagophore maturation; autophagosome formation; phosphorylation; Wipi2; Atg12-5-16L1 During autophagy specialized double membrane structures known as autophagosomes are formed that recruit the cargo to be degraded and deliver it to lysosomes [1]. The recruitment of cargo to the autophagosome needs interaction of LC3-II with specialized proteins known as autophagy receptors, which recognize the cargo [2].
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