Stress-induced phospho-ubiquitin formation causes parkin degradation

Lyudmila Kovalchuke; Eugene V. Mosharov; Oren A. Levy; Lloyd A. Greene

Our experiments with parkin point mutants reveal that parkin binding to stress-induced phospho-Ub is critical for its PINK1-dependent loss, while parkin phosphorylation, per se, is dispensable. The finding that S65A parkin was not protected from loss induced by any of the stressors we used was unexpected because phosphorylation of S65 increases the binding affinity of parkin for phospho-Ub [46] , [47] , [79] , [81] . Given the importance of phospho-Ub binding for parkin loss, we anticipated that S65A parkin would exhibit greater protection from stressinduced degradation due to a lower affinity for phospho-Ub. On the contrary, both wild-type and S65A parkin were equally depleted under the conditions of our studies, though we cannot rule out the possibility that wild-type parkin is lost more rapidly in response to stress than the S65A