Reactome | PRKN binds p-S-Ub:MOM proteins

PRKN binds p-S-Ub:MOM proteins

Stable Identifier

R-HSA-9835009

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

mitochondrial outer membrane

ReviewStatus

3/5

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A loss in mitochondrial membrane potential leads to the PINK1-dependent recruitment of the E3 ubiquitin (Ub) protein ligase Parkin (PRKN) to the mitochondrial outer membrane (MOM) (Matsuda N et al., 2010; Narendra DP et al., 2010; VivesBauza C et al., 2010). This process is facilitated by the PINK1-mediated phosphorylation of preexisting Ub moieties on MOM proteins (Kane LA et al., 2014; Koyano F et al., 2014; ShibaFukushima K et al., 2014; Ordureau A et al., 2015; Kazlauskaite A et al., 2014; Zittlau K et al., 2022). PRKN binds to phosphorylated Ub moieties (Kazlauskaite A et al., 2015; Ordureau A et al., 2015) and this binding initiates a release of the intramolecular inhibitory interaction between the RING1 domain and the ubiquitin-like (UBL) domain of PRKN (Kumar A et al., 2015, 2017). The released UBL of PRKN is phosphorylated at the S65 residue by PINK1 (Kazlauskaite A et al., 2015; Sauvé V et al., 2015). The phosphorylation-induced conformational changes in PRKN enhance its E3 Ub ligase activity (Iguchi M et al., 2013; Kondapalli C et al., 2012; Caulfield TR et al., 2014; Tang MY et al., 2017). Activated PRKN catalyzes the attachment of monoUb and/or polyUb chains to various mitochondrial proteins, marking them either for degradation via the proteasome or promoting selective removal of damaged organelles through autophagy (mitophagy).

Literature References

PubMed ID	Title	Journal	Year
24751536	PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity Kane, LA, Lazarou, M, Fogel, AI, Li, Y, Yamano, K, Sarraf, SA, Banerjee, S, Youle, RJ	J Cell Biol	2014
20126261	PINK1 is selectively stabilized on impaired mitochondria to activate Parkin Narendra, DP, Jin, SM, Tanaka, A, Suen, DF, Gautier, CA, Shen, J, Cookson, MR, Youle, RJ	PLoS Biol.	2010
24660806	Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65 Kazlauskaite, A, Kondapalli, C, Gourlay, R, Campbell, DG, Ritorto, MS, Hofmann, K, Alessi, DR, Knebel, A, Trost, M, Muqit, MM	Biochem J	2014
25969509	Defining roles of PARKIN and ubiquitin phosphorylation by PINK1 in mitochondrial quality control using a ubiquitin replacement strategy Ordureau, A, Heo, JM, Duda, DM, Paulo, JA, Olszewski, JL, Yanishevski, D, Rinehart, J, Schulman, BA, Harper, JW	Proc Natl Acad Sci U S A	2015
25284222	Quantitative proteomics reveal a feedforward mechanism for mitochondrial PARKIN translocation and ubiquitin chain synthesis Ordureau, A, Sarraf, SA, Duda, DM, Heo, JM, Jedrychowski, MP, Sviderskiy, VO, Olszewski, JL, Koerber, JT, Xie, T, Beausoleil, SA, Wells, JA, Gygi, SP, Schulman, BA, Harper, JW	Mol Cell	2014
24784582	Ubiquitin is phosphorylated by PINK1 to activate parkin Koyano, F, Okatsu, K, Kosako, H, Tamura, Y, Go, E, Kimura, M, Kimura, Y, Tsuchiya, H, Yoshihara, H, Hirokawa, T, Endo, T, Fon, EA, Trempe, JF, Saeki, Y, Tanaka, K, Matsuda, N	Nature	2014
25474007	Phosphorylation of mitochondrial polyubiquitin by PINK1 promotes Parkin mitochondrial tethering Shiba-Fukushima, K, Arano, T, Matsumoto, G, Inoshita, T, Yoshida, S, Ishihama, Y, Ryu, KY, Nukina, N, Hattori, N, Imai, Y	PLoS Genet	2014
35491809	Structural basis for feedforward control in the PINK1/Parkin pathway Sauvé, V, Sung, G, MacDougall, EJ, Kozlov, G, Saran, A, Fakih, R, Fon, EA, Gehring, K	EMBO J	2022
26116755	Binding to serine 65-phosphorylated ubiquitin primes Parkin for optimal PINK1-dependent phosphorylation and activation Kazlauskaite, A, Martínez-Torres, RJ, Wilkie, S, Kumar, A, Peltier, J, Gonzalez, A, Johnson, C, Zhang, J, Hope, AG, Peggie, M, Trost, M, van Aalten, DM, Alessi, DR, Prescott, AR, Knebel, A, Walden, H, Muqit, MM	EMBO Rep	2015