Dynamic disorder is crucial for mitochondrial protein import Schneider, Jakob Guillerm, Undina Simoes Pereira, Caroline Schanda, Paul ; https://orcid.org/0000-0002-9350-7606 ddc:572 The import of proteins into mitochondria poses fundamental mechanistic challenges: aggregation-prone precursor proteins must be maintained in aqueous compartments and threaded through narrow pores without becoming stuck or mislocalized. Recent evidence from mitochondrial protein import studies and other chaperone systems underscores the critical role of dynamics in balancing sufficiently tight binding, promiscuity, specificity, and release. Dynamic binding of client precursor proteins to import machinery components arises naturally from the avidity of their interactions. Conformational entropy enhances their stability, while the multivalent nature of these interactions ensures that client transfer to downstream insertases occurs without a substantial energy barrier. Here, we discuss this emerging paradigm of dynamic protein handling, using examples where dynamic structures have been resolved and highlight outstanding questions. Wiley 2026 info:eu-repo/semantics/article doc-type:article text http://purl.org/coar/resource_type/c_2df8fbb1 https://research-explorer.ista.ac.at/record/21929 https://research-explorer.ista.ac.at/download/21929/21937 Schneider J, Guillerm U, Simoes Pereira C, Schanda P. Dynamic disorder is crucial for mitochondrial protein import. <i>Protein Science</i>. 2026;35(6). doi:<a href="https://doi.org/10.1002/pro.70630">10.1002/pro.70630</a> eng info:eu-repo/semantics/altIdentifier/doi/10.1002/pro.70630 info:eu-repo/semantics/altIdentifier/issn/0961-8368 info:eu-repo/semantics/altIdentifier/e-issn/1469-896X info:eu-repo/semantics/altIdentifier/pmid/42159315 https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess