Reactome | TBK1 is phosphorylated within TBK1:OPTN:Ub-mitochondrial proteins

TBK1 is phosphorylated within TBK1:OPTN:Ub-mitochondrial proteins

Stable Identifier

R-HSA-9824894

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, mitochondrial outer membrane

ReviewStatus

3/5

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TBK1 is phosphorylated within TBK1:OPTN:Ub-mitochondrial proteins

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Upon mitochondrial damage, TANK-binding kinase 1 (TBK1) is recruited to the damaged mitochondria through a direct interaction with the autophagy receptor optineurin (OPTN) (Heo JM et al., 2015; Richter B et al., 2016). Once at the mitochondria, TBK1 undergoes phosphorylation at S172 within the activation loop (Heo JM et al., 2015; Richter B et al., 2016). The phosphorylation of TBK1 is a crucial step in its activation (Ma X et al., 2012). Mitochondria-bound active TBK1, in turn, phosphorylates OPTN (Richter B et al., 2016) and other autophagy adaptors (Matsumoto G et al., 2015) thereby facilitating selective autophagy of damaged mitochondria. Several loss-of-function mutations in the TBK1 gene may contribute to pathology of neurodegenerative disorders due to impaired autophagy (Li F et al., 2018; Harding O et al., 2021).

Literature References

PubMed ID	Title	Journal	Year
26365381	The PINK1-PARKIN Mitochondrial Ubiquitylation Pathway Drives a Program of OPTN/NDP52 Recruitment and TBK1 Activation to Promote Mitophagy Heo, JM, Ordureau, A, Paulo, JA, Rinehart, J, Harper, JW	Mol Cell	2015
38287189	Optineurin provides a mitophagy contact site for TBK1 activation Yamano, K, Sawada, M, Kikuchi, R, Nagataki, K, Kojima, W, Endo, R, Kinefuchi, H, Sugihara, A, Fujino, T, Watanabe, A, Tanaka, K, Hayashi, G, Murakami, H, Matsuda, N	EMBO J	2024
27035970	Phosphorylation of OPTN by TBK1 enhances its binding to Ub chains and promotes selective autophagy of damaged mitochondria Richter, B, Sliter, DA, Herhaus, L, Stolz, A, Wang, C, Beli, P, Zaffagnini, G, Wild, P, Martens, S, Wagner, SA, Youle, RJ, Dikic, I	Proc Natl Acad Sci U S A	2016