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Comment
. 2017 Jun;33(3):354-356.
doi: 10.1007/s12264-017-0116-3. Epub 2017 Mar 7.

The TBK1-OPTN Axis Mediates Crosstalk Between Mitophagy and the Innate Immune Response: A Potential Therapeutic Target for Neurodegenerative Diseases

Lu He  1 , Linxi Chen  2 , Lanfang Li  3   4
Affiliations
Comment

The TBK1-OPTN Axis Mediates Crosstalk Between Mitophagy and the Innate Immune Response: A Potential Therapeutic Target for Neurodegenerative Diseases

Lu He et al. Neurosci Bull. 2017 Jun.
No abstract available

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Figures

Fig. 1
Fig. 1
TBK1-OPTN axis facilitates the turnover of impaired mitochondria via mitophagy. Step 1. Mitochondrial damage leads to depolarization induced by the uncoupler carbonyl-cyanide m-chlorophenyl-hydrazine. Step 2. Accumulation of PINK1 (PTEN-induced putative kinase 1) recruits the E3 ubiquitin ligase parkin, contributing to the ubiquitination of outer mitochondrial membrane proteins. Step 3. PINK1-parkin activation promotes TBK1 phosphorylation of S172 on mitochondria. TBK1 phosphorylates OPTN at Ser177, Ser473, and Ser513, thereby enhancing the capacity of OPTN to bind to poly-Ub chains. In turn, poly-Ub chain binding to OPTN is required for TBK1 recruitment and activation on mitochondria. Step 4. Thus, the TBK1-OPTN axis promotes autophagosome formation around damaged mitochondria via the LC3-interacting domain (LIR) and is sufficient for mitophagy.
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References

    1. Richter B, Sliter DA, Herhaus L, Stolz A, Wang C, Beli P, et al. Phosphorylation of OPTN by TBK1 enhances its binding to Ub chains and promotes selective autophagy of damaged mitochondria. Proc Natl Acad Sci USA. 2016;113:4039–4044. doi: 10.1073/pnas.1523926113. - DOI - PMC - PubMed
    1. Heo JM, Ordureau A, Paulo JA, Rinehart J, Harper JW. The PINK1-PARKIN mitochondrial ubiquitylation pathway drives a program of OPTN/NDP52 recruitment and TBK1 activation to promote mitophagy. Mol Cell. 2015;60:7–20. doi: 10.1016/j.molcel.2015.08.016. - DOI - PMC - PubMed
    1. Moore AS, Holzbaur EL. Spatiotemporal dynamics of autophagy receptors in selective mitophagy. Autophagy. 2016;12:1956–1957. doi: 10.1080/15548627.2016.1212788. - DOI - PMC - PubMed
    1. Wong YC, Holzbaur EL. Temporal dynamics of PARK2/parkin and OPTN/optineurin recruitment during the mitophagy of damaged mitochondria. Autophagy. 2015;11:422–424. doi: 10.1080/15548627.2015.1009792. - DOI - PMC - PubMed
    1. Lazarou M, Sliter DA, Kane LA, Sarraf SA, Wang C, Burman JL, et al. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature. 2015;524:309–314. doi: 10.1038/nature14893. - DOI - PMC - PubMed

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