Club Mitochondrie - Eloina Corradi, Interdisciplinary Institute for Neuroscience, Bordeaux

Mitochondrial bioenergetic function is tightly coupled to organelle architecture, from cristae organization within the inner membrane to the large-scale morphology of the mitochondrial network. This structural adaptability relies on fission and fusion events, dedicated remodeling proteins, and membrane contact sites among other players, allowing mitochondria to adjust their organization to cellular metabolic demands. While mechanical stimuli are now recognized as important regulators of cellular metabolism, the mechanisms by which forces induce mitochondrial remodeling remain poorly understood.
We investigated whether mechanical forces directly influence mitochondrial organization and thereby contribute to the regulation of bioenergetic metabolism. Using a unique biomechanical device compatible with super-resolution microscopy, we show that a single mechanical stretch induces a rapid and profound reorganization of mitochondria across multiple spatial scales. At the network level, mechanical stimulation promotes mitochondrial fragmentation. At the nanoscale, this response is preceded by deformation of the outer mitochondrial membrane and accompanied by remodeling of the inner membrane architecture.
Overall, our results reveal that mechanical forces reorganize mitochondria from cristae to whole-organelle morphology with unprecedented spatiotemporal resolution. These findings position mitochondria as active mechanosensitive organelles and open new perspectives on the dialogue between cellular forces and mitochondrial architecture. In this view, mitochondria are not only targets of mechanical cues but may also feed back on the force-generating machinery by tuning the local bioenergetic and metabolic landscape.