Inhibitors of lysosomal function or serum starvation in control or LAMP2 deficient cells do not modify the cellular levels of Parkinson disease-associated DJ-1/PARK 7 protein

Mutations in PARK7/DJ-1 gene are associated with familial autosomal recessive Parkinson disease. Recently, lysosomes and chaperone mediated autophagy (CMA) has been reported to participate in the degradation of DJ-1/PARK7 protein. Lamp-2A isoform is considered as the lysosomal receptor for the uptake of proteins being degraded by the CMA pathway. We have used several cell lines with disrupted LAMP2 gene expression and their respective control cells to test the possible role of lysosomal degradation and in particular CMA in DJ-1/PARK7 degradation. Interruption of LAMP-2 expression did not result in an increase of the steady-state protein levels of DJ-1/PARK7, as it would have been expected. Furthermore, no change in DJ-1/PARK7 protein levels were observed upon inhibition of lysosomal function with NH4Cl or NH4Cl plus leupeptin, or after activation of CMA by serum starvation for 24h. Accordingly, we have not found any evidence that DJ-1/PARK7 protein levels are regulated via lysosomal degradation or the CMA pathway.