Emerging views of OPTN (optineurin) function in the autophagic process associated with disease

Abstract

Macroautophagy/autophagy is a highly conserved process in eukaryotic cells. It plays a critical role in cellular homeostasis by delivering cytoplasmic cargos to lysosomes for selective degradation. OPTN (optineurin), a well-recognized autophagy receptor, has received considerable attention due to its multiple roles in the autophagic process. OPTN is associated with many human disorders that are closely related to autophagy, such as rheumatoid arthritis, osteoporosis, and nephropathy. Here, we review the function of OPTN as an autophagy receptor at different stages of autophagy, focusing on cargo recognition, autophagosome formation, autophagosome maturation, and lysosomal quality control. OPTN tends to be protective in most autophagy associated diseases, though the molecular mechanism of OPTN regulation in these diseases is not well understood. A comprehensive review of the function of OPTN in autophagy provides valuable insight into the pathogenesis of human diseases related to OPTN and facilitates the discovery of potential key regulators and novel therapeutic targets for disease intervention in patients with autophagic diseases. Abbreviations: ATG: autophagy-related; APAP: acetaminophen; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CC: coiled-coil; HACE1: HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1; MYO6: myosin VI; IKBKG/NEMO: inhibitor of nuclear factor kappa B kinase regulatory subunit gamma; IKK: IκB kinase; LIR: LC3-interacting region; LZ: leucine zipper; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; NFKB/NF-κB: nuclear factor kappa B subunit; OPTN: optineurin; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; RTECs: renal tubular epithelial cells; SQSTM1/p62: sequestosome 1; TBK1: TANK binding kinase 1; TOM1: target of myb1 membrane trafficking protein; UBD: ubiquitin-binding domain; ULK1: unc-51 like autophagy activating kinase 1; WIPI2: WD repeat domain, phosphoinositide interacting 2; ZF: zinc finger.