Stress-induced phospho-ubiquitin formation causes parkin degradation

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

Phospho-Ub-dependent parkin loss does not require parkin autoubiquitination Of note, given that parkin has been shown to only autoubiquitinate in cis [98] , the finding that C431S parkin was not protected from L-DOPA-induced depletion indicates that this loss is not due to autoubiquitination. Parkin autoubiquitination has been reported following mitochondrial depolarization, reflected by the formation of higher-molecular weight parkin species as detected by WB [36] , [40] , [99] [100] [101] . It was previously suggested that such autoubiquitination is what targets parkin for proteasomal degradation following mitochondrial depolarization [40] . In the studies where parkin autobiquitination was observed, the ubiquitinated parkin signal was generally strongest for the band corresponding to mono-ubiquitinated parkin, but multiply-ubiquitinated parkin species were also detected, though with diminished intensity.