article published yes Jakob Schneider author 64368429-eb97-11eb-a6c2-c980b1f44415 Undina Guillerm author bb74f472-ae54-11eb-9835-bc9c22fb1183 Caroline Simoes Pereira author 87266c4a-96d2-11ef-be2c-fe5633233ec3 Paul Schanda author 7B541462-FAF6-11E9-A490-E8DFE56974250000-0002-9350-7606 GradSch department PaSc department Structure and mechanism of the mitochondrial MIM insertase project 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. https://research-explorer.ista.ac.at/download/21929/21937/2026_ProteinScience_Schneider.pdf application/pdfno https://creativecommons.org/licenses/by/4.0/ Wiley2026 eng 0961-8368 1469-896X 4215931510.1002/pro.70630 356 Schneider, Jakob, et al. “Dynamic Disorder Is Crucial for Mitochondrial Protein Import.” <i>Protein Science</i>, vol. 35, no. 6, e70630, Wiley, 2026, doi:<a href="https://doi.org/10.1002/pro.70630">10.1002/pro.70630</a>. 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> Schneider J, Guillerm U, Simoes Pereira C, Schanda P. 2026. Dynamic disorder is crucial for mitochondrial protein import. Protein Science. 35(6), e70630. J. Schneider, U. Guillerm, C. Simoes Pereira, and P. Schanda, “Dynamic disorder is crucial for mitochondrial protein import,” <i>Protein Science</i>, vol. 35, no. 6. Wiley, 2026. Schneider, J., Guillerm, U., Simoes Pereira, C., &#38; Schanda, P. (2026). Dynamic disorder is crucial for mitochondrial protein import. <i>Protein Science</i>. Wiley. <a href="https://doi.org/10.1002/pro.70630">https://doi.org/10.1002/pro.70630</a> Schneider, Jakob, Undina Guillerm, Caroline Simoes Pereira, and Paul Schanda. “Dynamic Disorder Is Crucial for Mitochondrial Protein Import.” <i>Protein Science</i>. Wiley, 2026. <a href="https://doi.org/10.1002/pro.70630">https://doi.org/10.1002/pro.70630</a>. J. Schneider, U. Guillerm, C. Simoes Pereira, P. Schanda, Protein Science 35 (2026). 219292026-05-31T22:02:12Z2026-06-02T07:26:34Z