AbstractPeroxisome biogenesis diseases (PBDs) are characterized by global defects in peroxisomal function and can result in severe brain, liver, kidney, and bone malfunctions. PBDs are due to mutations in peroxisome biogenesis factors (PEX genes) that are responsible for peroxisome assembly and function. There is increasing evidence suggesting that peroxisome import functions decline during aging. The transcriptome profiling of peroxisome import defects is still lacking. To identify conserved responses, we undertook a bioinformatic transcriptomic analysis on Drosophila oenocyte specific Pex1, Pex12 and Pex5 knockdowns. In addition, we performed analysis on human cells with induced peroxisome import stress. We uncovered that oenocyte-specific Pex1, Pex12 and Pex5 have distinct transcriptional profiles with each other. Using gene set enrichment analysis (GSEA), we identified protein processing in endoplasmic reticulum pathway, specifically ER-associated protein degradation (ERAD) pathway is enriched and induced in all PEX knockdowns in Drosophila. Moreover, we uncovered decreased expression in ribosome biogenesis genes in flies and human cells. Indeed, we identified a stall at the 5’-ETS cleavage sites during the ribosome biogenesis and impaired 40S small ribosomal export in both flies and human. Our data indicates an unexpected link between peroxisome and ribosome biogenesis. Our results suggest that reduced ribosome biogenesis could be conserved cellular response to reduce peroxisome import stress.
Peroxisome Biogenesis and Function
