Lysosomal inhibition attenuates peroxisomal gene transcription via suppression of PPARA and PPARGC1A levels.

ABSTRACT: Lysosomes influence dynamic cellular processes such as nutrient sensing and transcriptional regulation. To explore novel transcriptional pathways regulated by lysosomes, we performed microarray analysis followed by qPCR validation in a mouse hepatocyte cell line, AML12, treated with bafilomycin A₁ (lysosomal v-type H⁺-translocating ATPase inhibitor). Pathway enrichment analysis revealed significant downregulation of gene sets related to peroxisomal biogenesis and peroxisomal lipid oxidation upon lysosomal inhibition. Mechanistically, pharmacological inhibition of lysosomes as well as genetic knockdown of Tfeb led to downregulation of the peroxisomal master regulator PPARA and its coactivator PPARGC1A/PGC1α. Consistently, ectopic induction of PPARA transcription

SUBMITTER: Tan HWS 

PROVIDER: S-EPMC6613898 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature