Mitochondrial respiratory chain dysfunction alters ER sterol sensing and mevalonate pathway activity.

ABSTRACT: Mitochondrial dysfunction induces a strong adaptive retrograde signaling response; however, many of the downstream effectors of this response remain to be discovered. Here, we studied the shared transcriptional responses to three different mitochondrial respiratory chain inhibitors in human primary skin fibroblasts using QuantSeq 3'-RNA-sequencing. We found that genes involved in the mevalonate pathway were concurrently downregulated, irrespective of the respiratory chain complex affected. Targeted metabolomics demonstrated that impaired mitochondrial respiration at any of the three affected complexes also had functional consequences on the mevalonate pathway, reducing levels of cholesterol precursor metabolites. A deeper study of complex I inhibition showed a reduced activity of endoplasm

SUBMITTER: Wall CTJ 

PROVIDER: S-EPMC8892029 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature