PRKN binds p-S-Ub:MOM proteins

Stable Identifier
R-HSA-9835009
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
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

Li, Y, Sarraf, SA, Fogel, AI, Kane, LA, Banerjee, S, Lazarou, M, Youle, RJ, Yamano, K

J Cell Biol 2014
20126261 PINK1 is selectively stabilized on impaired mitochondria to activate Parkin

Tanaka, A, Jin, SM, Cookson, MR, Narendra, DP, Suen, DF, Shen, J, Youle, RJ, Gautier, CA

PLoS Biol. 2010
24660806 Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65

Ritorto, MS, Campbell, DG, Kazlauskaite, A, Alessi, DR, Gourlay, R, Hofmann, K, Knebel, A, Kondapalli, C, Muqit, MM, Trost, M

Biochem J 2014
25969509 Defining roles of PARKIN and ubiquitin phosphorylation by PINK1 in mitochondrial quality control using a ubiquitin replacement strategy

Duda, DM, Paulo, JA, Schulman, BA, Heo, JM, Yanishevski, D, Ordureau, A, Harper, JW, Rinehart, J, Olszewski, JL

Proc Natl Acad Sci U S A 2015
25284222 Quantitative proteomics reveal a feedforward mechanism for mitochondrial PARKIN translocation and ubiquitin chain synthesis

Jedrychowski, MP, Duda, DM, Schulman, BA, Gygi, SP, Heo, JM, Sviderskiy, VO, Ordureau, A, Harper, JW, Beausoleil, SA, Sarraf, SA, Xie, T, Koerber, JT, Wells, JA, Olszewski, JL

Mol Cell 2014
24784582 Ubiquitin is phosphorylated by PINK1 to activate parkin

Endo, T, Kimura, Y, Fon, EA, Tamura, Y, Go, E, Hirokawa, T, Trempe, JF, Saeki, Y, Kosako, H, Yoshihara, H, Okatsu, K, Kimura, M, Tsuchiya, H, Tanaka, K, Matsuda, N, Koyano, F

Nature 2014
25474007 Phosphorylation of mitochondrial polyubiquitin by PINK1 promotes Parkin mitochondrial tethering

Matsumoto, G, Nukina, N, Inoshita, T, Imai, Y, Shiba-Fukushima, K, Ishihama, Y, Arano, T, Ryu, KY, Hattori, N, Yoshida, S

PLoS Genet 2014
35491809 Structural basis for feedforward control in the PINK1/Parkin pathway

Fon, EA, Saran, A, Kozlov, G, Fakih, R, MacDougall, EJ, Gehring, K, Sung, G, Sauvé, V

EMBO J 2022
26116755 Binding to serine 65-phosphorylated ubiquitin primes Parkin for optimal PINK1-dependent phosphorylation and activation

Martínez-Torres, RJ, Trost, M, Wilkie, S, Zhang, J, Hope, AG, Prescott, AR, Kazlauskaite, A, Peltier, J, Alessi, DR, Gonzalez, A, van Aalten, DM, Peggie, M, Knebel, A, Kumar, A, Muqit, MM, Walden, H, Johnson, C

EMBO Rep 2015
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