Project B12 will elucidate the mechanisms mediating dynamic remodeling of the cristae membrane within mitochondria. The ultrastructure of the cristae membrane is highly variable and strongly altered in numerous human disorders. Remodelling of this membrane is known for more than 50 years (condensed vs. orthodox state) and was shown to occur also during apoptosis. The MICOS (‘Mitochondrial Contact Site and Cristae Organizing System’) complex is a large membrane protein complex ensuring proper cristae membrane architecture. By using live-cell stimulated emission depletion (STED) nanoscopy we could show for the first time that cristae membranes are highly dynamic and are reorganising themselves at a time scale of seconds in a MICOS-dependent manner. In this project, we aim to get a molecular understanding of the mechanisms and the physiological function of MICOS-dependent cristae membrane dynamics in mammalian cells. To achieve these aims we will apply nanoscopic techniques in living mammalian cells in combination with biochemical and genetic methods.