Mitochondrial morpho-functional remodeling in MechanoMetabolism: sensing force, changing shape, modulating bioenergetic metabolism - Eloina Corradi (MICROTISS)

Mitochondria are double-membrane organelles that sustain the bioenergetic metabolism of cells by producing ATP at the level of the cristae, convoluted folds of the inner membrane. ATP production efficiency and mitochondrial morphology, including cristae architecture, are tightly linked. Consequently, by being coupled to mitochondrial function, the reshaping of mitochondria across spatial scales regulates the cellular bioenergetic and metabolic states. Mechanical stimuli have recently been shown to modulate cellular metabolism, thus impacting physiological (e.g. cell migration, proliferation, death) and pathological (e.g. cancer progression) processes.

By using a unique biomechanical tool to stretch cells compatible with super-resolution microscopy, we were able to show that mechanical stimulation drastically re-shape mitochondria at the nanoscale level. In particular, we observed that mitochondrial outer membrane is reshaped upon mechanical stretch, with several constriction regions along mitochondria and with a reshuffle also of the mitochondrial-nanotunnels network. Moreover, also the inner membrane was drastically deformed, with a mechanical-driven remodeling of mitochondrial cristae. At the macro-scale, a single mechanical stretch was sufficient to induce Drp1-dependent mitochondrial fission and by tracking Drp1 single molecule through sptPALM during mechanical stimulation revealed an increase recruitment of the protein during stretch. Overall, we show how mechanical forces reshape mitochondria at a spatiotemporal resolution never tackled before, further opening the horizon of mechano-metabolism based on cellular organelle re-shaping.