Sylviane Metairon

Abstract Skeletal muscle relies on resident muscle stem cells (MuSCs) for growth and repair. Aging and muscle diseases impair MuSC function, leading to stem cell exhaustion and regenerative decline that contribute to the progressive loss of skeletal muscle mass and strength.

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.

Experimental procedures Reagents and chemicals Unless otherwise stated, all chemicals were from purchased from Merck KGaA (formerly Sigma Aldrich). Phosphate buffered saline ( pH 7.4) was purchased from Thermo Fischer (Gibco, cat# 10010023). Cyclodextrin loading A stock solution of 5% methyl-beta-cyclodextrins was prepared by dissolving in ultrapure water. A stock solution of 1% cholesterol was made in methanol: chloroform (2:1).