P 238 - Mitochondrial adaptive response in a model of CoQ10 deprived human dermal fibroblasts

Abstract

CoQ10 is a ubiquitous isoprenilated quinone with a key role in cellular bioenergetic and as antioxidant in membranes. The organism produces adequate amount to support physiologic demand although biosynthesis could be influenced by genetic background, nutrition and lifestyle. Moreover, ageing and of HMG-CoA reductase inhibitors may play an important role in further lowering synthesis. At skin level CoQ10 decrease is known to be associated with senescence manifestation. In the present study we developed a model of CoQ10 deprivation in human dermal fibroblast to mimic processes associated with ageing in order to elucidate the role of this cofactor in mitochondrial remodeling and adaptive response. Flow cytometric analysis of mitochondrial function and ROS production was associated with respirometry profiling and molecular markers of mitochondrial biogenesis in cells exposed for 72hrs to a log range of simvastatin concentrations. Analysis outlined a series of complex adaptative response where statin dose dependently affected CoQ10 levels and oxidative status steering either hormetic responses or mitochondrial PTP opening associated to selective elimination of defective mitochondria or overt cellular toxicity stressing the central role of this molecule in the biochemistry of cell ageing