Parkinson disease (PD) is the most common neurodegenerative movement disorder. 
An increase in the amount of alpha-synuclein protein could constitute a cause of 
PD. Alpha-synuclein is degraded at least partly by chaperone-mediated autophagy 
(CMA). The I93M mutation in ubiquitin C-terminal hydrolase L1 (UCH-L1) is 
associated with familial PD. However, the relationship between alpha-synuclein 
and UCH-L1 in the pathogenesis of PD has remained largely unclear. In this 
study, we found that UCH-L1 physically interacts with LAMP-2A, the lysosomal 
receptor for CMA, and Hsc70 and Hsp90, which can function as components of the 
CMA pathway. These interactions were abnormally enhanced by the I93M mutation 
and were independent of the monoubiquitin binding of UCH-L1. In a cell-free 
system, UCH-L1 directly interacted with the cytosolic region of LAMP-2A. 
Expression of I93M UCH-L1 in cells induced the CMA inhibition-associated 
increase in the amount of alpha-synuclein. Our findings may provide novel 
insights into the molecular links between alpha-synuclein and UCH-L1 and suggest 
that aberrant interaction of mutant UCH-L1 with CMA machinery, at least partly, 
underlies the pathogenesis of PD associated with I93M UCH-L1.