Optineurin: The autophagy connection

• Optineurin is a gene linked to normal tension glaucoma and amyotrophic lateral sclerosis.
• Autophagy is an intracellular degradation system that delivers cytoplasmic components to the lysosomes for degradation.
• Containing ubiquitin binding and LC3 interacting domains, the optineurin protein is a selective autophagy receptor.
• Optineurin acts as an autophagy receptor either via ubiquitin-dependent mechanisms or in an ubiquitin-independent manner.
• Optineurin can also be an autophagy inducer, inducing autophagic process upon overexpression and mutation.

Optineurin is a cytosolic protein encoded by the OPTN gene. Mutations of OPTN are associated with normal tension glaucoma and amyotrophic lateral sclerosis. Autophagy is an intracellular degradation system that delivers cytoplasmic components to the lysosomes. It plays a wide variety of physiological and pathophysiological roles. The optineurin protein is a selective autophagy receptor (or adaptor), containing an ubiquitin binding domain with the ability to bind polyubiquitinated cargoes and bring them to autophagosomes via its microtubule-associated protein 1 light chain 3-interacting domain. It is involved in xenophagy, mitophagy, aggrephagy, and tumor suppression. Optineurin can also mediate the removal of protein aggregates through an ubiquitin-independent mechanism. This protein in addition can induce autophagy upon overexpression or mutation. When overexpressed or mutated, the optineurin protein also serves as a substrate for autophagic degradation. In the present review, the multiple connections of optineurin to autophagy are highlighted.