Overcoming the “Resolution Gap”: Combining Super-Resolution Microscopy and Cryo-Electron Tomography to Identify Mitochondrial Vimentin Binding Sites

Progress in fundamental research is directly linked to the emergence of new methods that not only expand established classical concepts but can also provide information that fundamentally changes them. According to the authors’ data, vimentin filaments, by binding to mitochondria, determine their distribution and motility within cells and influence their membrane potential. Furthermore, the N-terminal region of the vimentin molecule contains a region responsible for the interaction of vimentin filaments with mitochondria, and similar amino acid sequences have been found in other proteins. Since direct interaction of vimentin filaments with microtubules and actin filaments has already been demonstrated, these facts taken together led the authors to hypothesize that the communication between individual cytoskeletal components and mitochondria is not limited to interactions via cross-linking and motor proteins. Vimentin (and possibly other intermediate filament proteins) may regulate the interaction of the cytoskeleton with mitochondria. A groundbreaking study using cryo-electron tomography, which fundamentally changed our understanding of the three-dimensional structure of vimentin filaments, prompted us to utilize cryo-electron microscopy to attempt to identify the binding sites of vimentin with other cytoskeletal components and mitochondria. This task could be solved by combining super-resolution microscopy and cryo-electron tomography, which would bridge the existing “resolution gap” and address associated challenges.