Mechanisms of mitochondrial protein translocation and membrane biogenesis
Pragya Kaushik — Hector Fellow Nikolaus Pfanner
Mitochondrial protein import is mediated by the presequence translocase of the inner membrane (TIM23 complex). While Tim17 is central for inner membrane translocation, the exact role of Mgr2, a small transmembrane protein, remains unclear. This project aims to define the function of Mgr2 in precursor protein import, membrane insertion, and translocase stability using genetic, biochemical, and structural approaches.
Mitochondria possess an intricate machinery for the import of nuclear-encoded mitochondrial proteins. The presequence translocase of the inner mitochondrial membrane is essential for importing presequence-containing precursor proteins into the mitochondrial matrix or inner membrane. While Tim17 forms a central part of the translocation pathway across the inner membrane, Mgr2, a small transmembrane protein, has been suggested to play a role in precursor protein translocation, inner membrane insertion, and presequence translocase stability. However, its exact functions remain unclear.
This research aims to clarify the role of Mgr2 in precursor protein import and its interaction with Tim17. Using genetic, biochemical, and structural approaches, we will generate Mgr2-Tim17 covalent linkages, study precursor protein translocation through import assays, and analyse presequence translocase stability via mutant strains. Furthermore, we will explore Mgr2’s role in transmembrane precursor insertion, the function of the hydrophobic plug of the translocation cavity, and the impact of presequence modifications on the import efficiency.
By uncovering Mgr2’s precise function, this study will contribute to our understanding of mitochondrial protein biogenesis and quality control, providing insights into potential mitochondrial disorders linked to import defects.
Pragya Kaushik
University of FreiburgSupervised by
Nikolaus Pfanner
Biology & ChemistryHector Fellow since 2011