Decipher molecular mechanisms responsible for mitochondrial dysfunction leading to motor neuron death. 2022-2025, FRM-Maladies neurodégénératives, PI Véronique Paquis-Flucklinger

The project aims to understand the molecular basis of motor neuron death caused by CHCHD10 mutations. We will explore the hypothesis that respiratory chain deficiency, loss of mitochondrial cristae and destabilization of the inner membrane structure within mitochondria lead to neuromuscular dysfunction and neuronal death. Using the cell and animal models we have generated, this project wants to (i) understand the role of CHCHD10 and the molecular pathways leading to MND, (ii) define the tissue and genetic interactions leading to neuronal death, and (iii) search for CHCHD10 modifier genes in patient-derived cell models.