Mitochondria rely on the efficient import of proteins to maintain their functions and regenerate. The translocase of the outer mitochondrial membrane (TOM) complex serves as the primary entry point for the import of mitochondrial proteins. Previous studies have established Tom22 as a multifunctional subunit within the complex and reported mechanosensitive gating-like behavior of the TOM complex. In this study, all-atom molecular dynamics simulations of the TOM core complex reveal large motions of the Tom22 helices that are coupled to global structural rearrangements within the complex, particularly with the α2 helix within the Tom40 pore subunit. Microseconds-long simulations with restraints on the Tom22 helices yield an alternative conformation of the α2 helix that is associated with a reduced ion permeability. The outcome corroborates previous experimental results that reported a reduction in calcium ion flux for transiently stalled TOM complexes. These findings provide a molecular view of a mechanism by which Tom22 modulates the pore architecture of Tom40 and regulates permeability, thus linking the receptor dynamics to the functional control of the mitochondrial protein import.

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Journal Article

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Acharya A, Nussberger S, Wang S, Kleinekathöfer U

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