CoQ deficiencies are a group of heterogeneous mitochondrial diseases characterized by a depletion in the CoQ level. CoQ is synthesized inside mitochondria where it participates in oxidative phosphorylation to generate ATP. Many genes are directly or indirectly involved in the mitochondrial synthesis of CoQ. It can be caused by defects in genes that are part of the CoQ10 synthesis complex or in its regulation inside mitochondria (primary deficiency), or as a secondary effect due to the alteration of other mitochondrial functions not directly involved in CoQ10 synthesis.
Any of these mutations induce depletion of CoQ levels, and cells retrain their metabolism to survive under defective mitochondria thanks to epigenetic modifications and changes in gene expression to generate a specific transcriptome for survival.
Human primary cell cultures obtained from patients with CoQ deficienciesallowed us to study these alterations in vitro, whereas animal models (mouse and fruit flies) permit us to study how an organism develops under CoQ depletion and how it ages prematurely.
We specifically studied muscle development in a mouse model of CoQ deficiency and characterized their defective mitochondria. Also, we are establishing different strategies to treat CoQ deficiency using these animal models.
We purify live mitochondria from muscle and study the differentiation process of muscle stem cells.