Centre de Biologie du Développement

Mitochondrial dynamics : from neurogenesis to neurodegeneration

Mitochondria morphology varies according to cell type and cellular context from an interconnected filamentous network to isolated dots. This morphological plasticity depends on mitochondrial dynamics, a balance between antagonistic forces of fission and fusion. DRP1 and FIS1 control mitochondria outer membrane fission and mitofusins its fusion. Our team has identified one of the few known actors of inner membrane dynamics, OPA1, which mutations provoke an optic neuropathy (type 1 Dominant Optic Atrophy, ADOA-1). During the last 5 years we focused our work on the molecular and functional characterization of OPA1 and of its yeast homologue Msp1, as well as on the pathophysiological mechanisms leading to ADOA-1. Mitochondrial dynamics influences the main functions of the organelle (respiration, calcium homeostasis, ROS production, apoptosis) and its distribution. Consequently, this phenomenon is due to play a major role in neurons because of their highly specialized nature and architecture as well as their plasticity during development and adulthood. A definite proof of the major role of mitochondrial dynamics in the nervous system came from the discovery that mutations in key actors of this process are responsible for neurodegenerative disorders. While pursuing our investigations on the influence of mitochondrial dynamics, and of OPA1, on neurodegeneration, we start now to study the impact of mitochondrial dynamics on the functions and plasticity of mature and developing neurons.