P 243 - Mitochondrial respiratory profile in human dermal fibroblast treated with HMG-coa reductase inhibitor

Abstract

Coenzyme Q10 is a endogenous isoprenilated quinone with antioxidant and bioenergetic activity. Its cellular levels and oxidative status are effected in ageing and synthetic rate is influenced by simvastatin, a widely used lipid lowering drug inhibiting HMG-coA reductase, a key enzyme in the mevalonate pathway. In light of its central role in mitochondrial bioenergetic and its relevance to the senescence process we evaluated how CoQ10 deprivation affected mitochondrial respiration in terms of oxygen consumption rate (OCR), evaluated using extracellular flux analyzer Seahorse bioscience, either in basal condition or following the incubation of selective inhibitors of different respiratory complexes. Human dermal fibroblast incubated at sublethal concentration of simvastatin, in the range 0.6 – 10 μM for 72 hours, showed a significant decrease in basal mitochondrial respiration at all tested concentrations associated with a significant decrease in ATP production. Moreover, at concentration higher than 2.5 μM significant decrease of maximal respiration and spare respiratory capacity suggest a decrease of the mitochondrial mass and/or poor ETC integrity that parallelled CoQ10 deprivation stressing the role of this molecule in cellular bioenergetic. Overall the data support the use of this experimental model for the study of age-related CoQ10 decrease in human skin.