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.