Abstract—
The role of intermediate filaments in the regulation of mitochondrial functions has become evident from recent studies. For example, vimentin has been shown to affect mitochondrial motility and the level of their membrane potential. However, the mechanism of their interaction is still largely unexplored. In particular, it is unknown whether vimentin can bind directly to mitochondria or whether any intermediate proteins are needed. In this study, using bioinformatics tools, we show that the vimentin sequence has a region in the N-terminal domain, which can play the role of a mitochondrial targeting peptide that probably directs vimentin to mitochondria and causes its binding with these organelles. In order to test this possibility, the binding of mitochondria isolated from rat liver with protofilaments formed by human recombinant vimentin was investigated using centrifugation through sucrose “cushion”. We demonstrate that vimentin can bind to mitochondria in vitro. We also show that the action of a mitochondrial protease leads to the loss of the N-terminal part of the vimentin molecule and its interaction with mitochondria is disrupted. Inhibitory analysis revealed that the atypical calpain, a cysteine Ca2+-dependent protease that is insensitive to the inhibitor calpastatin, is responsible for its degradation.
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This work was supported by the Russian Foundation for Basic Research (project no. 17-04-01775-a).
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All procedures were performed in accordance with the European Communities Council Directive (November 24, 1986; 86/609/EEC) and the Declaration on humane treatment of animals.
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Translated by A. Dayal
Abbreviations: IF, intermediate filaments; VIF, vimentin intermediate filaments; BCA, bicinchoninic acid; TOM, translocase of the outer membrane; TIM, translocase of the inner membrane; PAGE, polyacrylamide gel electrophoresis; PMSF, phenylmethylsulfonyl fluoride; SDS, sodium dodecyl sulfate.
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Dayal, A.A., Medvedeva, N.V. & Minin, A.A. N-Terminal Fragment of Vimentin Is Responsible for Binding of Mitochondria In Vitro. Biochem. Moscow Suppl. Ser. A 16, 151–157 (2022). https://doi.org/10.1134/S1990747822030059
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DOI: https://doi.org/10.1134/S1990747822030059