mRNA level of genes modulated by PARIS is down-regulated in GD fibroblasts or SHSY5Y cells expressing mutant GCase. (A) Under normal conditions, PARIS represses the expression of PGC1α, which leads to transcriptional inhibition of NRF1 and as a result also of ATPase5β. In GD derived cells, due to competition of PARIS with mutant GCase on parkin availability, a larger fraction of PARIS shuttles to the nucleus. As a result, there is a marked decrease in transcription of PGC1α, NRF1 and ATPase5β. (B) mRNA was extracted from normal or GD-derived fibroblasts and from SHSY5Y cells expressing normal or mutant GCase variants. It was subjected to quantitative real-time PCR analysis using primers specific for PGC1α, NRF1 or ATPase5β. The mRNA levels of PGC1α, NRF1 and ATPase5β are presented as a fold of decrease compared to that detected for normal fibroblasts. Values represent the mean ± SEM of 3–7 independent experiments. *P < 0.05, **P < 0.005, ***P < 0.001 in Student t-test. Numbers in parenthesis denote cell lines detailed in Table 1. Normal represents the average of cell lines 1 and 2 (Table 1).