Biophysical Society Conference | Tahoe 2022

Molecular Biophysics of Membranes

Poster Abstracts

30-POS Board 8 EXPLORING THE MECHANISM OF PROTEIN TRANSLOCATION ACROSS THE INNER MITOCHONDRIAL MEMBRANE D. L Lynch 1 ; S. I Sim 2,3 ; Y. Chen 2,3 ; E. Park 2,3 ; J. C Gumbart 1 ; 1 Georgia Institute of Technology, School of Physics, Atlanta, GA, USA 2 University of California, Department of Molecular and Cell Biology, Berkeley, CA, USA 3 University of California, California Institute for Quantitative Biosciences, Berkeley, CA, USA The majority of mitochondrial proteins are cytosolically translated and, therefore, require import across the outer and, depending on the destination, inner mitochondrial membranes (IMM). Protein translocases, multi-subunit complexes, recognize, import, and sort these precursor proteins. The TIM23 complex mediates import across the IMM into the matrix, as well as the IMM itself, and is comprised of the essential proteins Tim23, Tim17, and Tim44. Protein precursors are typically synthesized with a targeting signal, in the case of matrix proteins this is often a N-terminal basic, amphipathic stretch of amino-acids. As such the import of matrix proteins is thought to be partially driven by an electrophoretic force due to the inner membrane potential, which must be maintained for the respiration activity of mitochondria. Although the process of protein import across the IMM has been studied by a variety of biophysical approaches, the structural data necessary to parse the detailed translocation mechanism has been lacking. Moreover, it has recently been recognized that membrane thinning contributes to the process of retrotranslocation across the ER, suggesting an active role for the membrane itself in protein translocation processes. Recently, utilizing cryo-EM of the Tim23-Tim17-Tim44 complex and molecular dynamics simulations employing a realistic IMM membrane composition, we have begun to explore the roles that the membrane potential as well as membrane thinning play in the process of import across the IMM.

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