Séminaire thématique "Métabolisme énergétique et maladies rares"

Dr. Metodi M Metodiev (CRCN INSERM, INSERM UMR1163, Institut IMAGINE, Paris)

Mitochondrial diseases affect ~1 in 5000 live births and typically present soon after birth or during childhood though late-onset disease has also been reported. To date, more than 350 nuclear and most mitochondrial genes have been linked to mitochondrial diseases with variable clinical presentations. Though the brain and heart are frequently affected, other tissues and organs are also not spared. However, despite the ubiquitous expression of most genes encoding mitochondrial proteins, mitochondrial diseases can have an unexpected tissue specificity that remains unexplained to this day. At present, mitochondrial diseases are incurable whereas the few available treatments are symptomatic and cannot prevent the progression of the disease. Several factors contribute to this including our incomplete understanding of basic mitochondrial biology and disease pathomechanisms, as well as the general scarcity of model systems recapitulating basic pathophysiological features of mitochondrial disease in the context of differentiated tissues. Our interest lies in leveraging basic mitochondrial biology for uncovering different mitochondrial disease pathomechanisms and their characterization. Through our collaboration with physicians, we have identified several novel mitochondrial diseases genes involved in different aspects of mitochondrial gene expression and proteostasis including RNA metabolism, mitochondrial translation, and protein maturation. Our work has since focused on studying how inactivation of some these factors leads to mitochondrial dysfunction using cultured cells and animal models.