Cristae undergo continuous cycles of membrane remodelling in a MICOS‐dependent manner

• Published in: EMBO reports 2020-03, Vol.21 (3), p.e49776-n/a
• Main Authors: Kondadi, Arun Kumar, Anand, Ruchika, Hänsch, Sebastian, Urbach, Jennifer, Zobel, Thomas, Wolf, Dane M, Segawa, Mayuko, Liesa, Marc, Shirihai, Orian S, Weidtkamp‐Peters, Stefanie, Reichert, Andreas S
• Format: Article
• Language: English
• Subjects: crista junction; Cristae; Depletion; Docking; EMBO20; EMBO57; Fission; Fluorescence; Fluorescence recovery after photobleaching; HeLa Cells; Humans; Imaging techniques; Invaginations; Lipophilic; Mammalian cells; membrane dynamics; Membrane fusion; Membrane potential; Membranes; Mitochondria; Mitochondrial Membranes - metabolism; Mitochondrial Proteins - metabolism; Particle tracking; Photobleaching; STED nanoscopy; Stimulated emission; Variation
• ISSN: 1469-221X; 1469-3178
• DOI: 10.15252/embr.201949776

The mitochondrial inner membrane can reshape under different physiological conditions. How, at which frequency this occurs in living cells, and the molecular players involved are unknown. Here, we show using state‐of‐the‐art live‐cell stimulated emission depletion (STED) super‐resolution nanoscopy that neighbouring crista junctions (CJs) dynamically appose and separate from each other in a reversible and balanced manner in human cells. Staining of cristae membranes (CM), using various protein markers or two lipophilic inner membrane‐specific dyes, further revealed that cristae undergo continuous cycles of membrane remodelling. These events are accompanied by fluctuations of the membrane potential within distinct cristae over time. Both CJ and CM dynamics depended on MIC13 and occurred at similar timescales in the range of seconds. Our data further suggest that MIC60 acts as a docking platform promoting CJ and contact site formation. Overall, by employing advanced imaging techniques including fluorescence recovery after photobleaching (FRAP), single‐particle tracking (SPT), live‐cell STED and high‐resolution Airyscan microscopy, we propose a model of CJ dynamics being mechanistically linked to CM remodelling representing cristae membrane fission and fusion events occurring within individual mitochondria. Synopsis Mitochondrial crista junctions and cristae membranes undergo continuous remodelling events in a MICOS‐dependent manner. These findings, based on live‐STED nanoscopy and complementary approaches, change the dogma of cristae being static invaginations of the inner membrane and open a novel, highly dynamic view on the internal structure of mitochondria. Crista junctions (CJs) and cristae membranes (CM) undergo dynamic remodelling at a time‐scale of seconds in a reversible, balanced, and MICOS‐dependent manner. MIC60 is the primary docking site for formation of the MICOS complex to ensure CJ formation in mammalian cells. The mitochondrial membrane potential is shown to dynamically fluctuate in distinct cristae, which is correlated to CM remodelling events. We propose a model of CJ‐dynamics being mechanistically linked to CM remodelling representing cristae membrane fission and fusion events occurring within individual mitochondria. Graphical Abstract Live‐STED nanoscopy and complementary approaches reveal that mitochondrial crista junctions and cristae membranes are not static invaginations but highly dynamic, undergoing continuous remodeling events in