Optineurin (OPTN) is an ubiquitin (Ub)-binding adaptor protein, recruited to damaged mitochondria via the PINK1:PRKN-mediated ubiquitination of the mitochondrial substrates (Wong YC & Holzbaur EL 2014; Heo JM et al., 2015; Lazarou M et al., 2015; reviewed in Qiu Y et al., 2022). OPTN interacts with microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B or LC3B) via its LC3-interacting region (LIR) (Wild P et al., 2011; Wong YC & Holzbaur ELF 2014; Padman BS et al., 2019; Putyrski M et al., 2020). MAP1LC3B belongs to the LC3 subfamily of autophagy-related 8 (ATG8) proteins, which are recruited to an autophagopore to regulate autophagic membrane elongation. TANK-binding kinase 1 (TBK1)-mediated phosphorylation of OPTN at the Ser177 residue enhances the binding affinity of OPTN to MAP1LC3B (Wild P et al., 2011; Heo JM et al., 2015; Sirohi K et al., 2015; Moor AS & Holzbaur ELF 2016; Putyrski M et al., 2020). The OPTN binding to MAP1LC3B (LC3B) promotes the formation of LC3B-positive autophagosome around the damaged mitochondria (Wong YC Holzbaur ELF 2014; Heo JM et al., 2015). The mechanisms underlying the OPTN:MAP1LC3B-dependent autophagosomal engulfment of mitochondria have not been determined (Nguyan TN et al., 2016; Padman BS et al., 2019; Yamano K et al., 2020). On one hand, the LIR motif of OPTN recruits MAP1LC3B to the damaged mitochondria in a PINK1:PRKN-dependent manner (Wong YC Holzbaur ELF 2014; Heo JM et al., 2015). On the other hand, mitochondria-bound OPTN can recruit other ATG proteins other than MAP1LC3B (LC3) to promote selective autophagy of mitochondria in MAP1LC3B-independent manner (Yamano K et al., 2020). MAP1LC3B, like other ATG8 homologs, undergoes post-initiation lipidation on the expanding autophagophore, that leads to the additional recruitment of OPTN and other autophagy receptors through their LIR motif thus creating a positive feedback loop that accelerate autophagosome biogenesis (Padman BS et al., 2019).
This Reactome event shows interaction between mitochondria-bound OPTN and MAP1LC3B.
