Up-regulation of cholesterol synthesis by lysosomal defects requires a functional mitochondrial respiratory chain

To understand the common and opposite effects of mitochondrial and lysosomal perturbations on cellular signaling, we performed RNAseq in HeLa cells stably silenced for the mitochondrial respiratory chain subunit UQCRC1 (as a model of chronic mitochondrial respiratory chain deficiency), for lysosomal hydrolase acid alpla-glucosidase (GAA), or for lysosomal cathepsin B (CTSB). The controls were HeLa cells with scrambled shRNA. Overall design: Two lines of HeLa-scrambled, two lines of UQCRC1-kd (each with a different shRNA), two lines of GAA-kd (each a different shRNA) and two lines of CTSB-kd (each with a different shRNA).