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bioRxiv · 10.1101/2024.05.30.596364

The N-terminus of mitochondrial Mix17 is exposed to the cytosol in an energy dependent manner

Resch, M.·Frickel, J. S.·Wen, R. C. S.·Hell, K.·Harner, M. E.
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Abstract

Mitochondrial architecture and the contacts between the outer and the inner mitochondrial membrane depend on the mitochondrial contact site and cristae organizing system (MICOS) that is highly conserved from yeast to human. Mutations in the mammalian MICOS subunit Mic14/CHCHD10 have been linked to amyotrophic lateral sclerosis and frontotemporal dementia, indicating the importance of this protein. Mic14/CHCHD10 has a yeast ortholog, Mix17, a protein of unknown function, which has not been shown to interact with MICOS so far. As a first step to elucidate the function of Mix17 and its orthologs, we analyzed its interactions, biogenesis and mitochondrial sublocation. We report that Mix17 is no stable MICOS subunit in yeast. Our data suggest that Mix17 is the first Mia40 substrate in the mitochondrial outer membrane. Unlike all other Mia40 substrates, Mix17 spans the outer membrane and exposes its N-terminus to the cytosol. The insertion of Mix17 is likely to be mediated by its interaction with Tom40, the pore of the TOM complex. Moreover, we show that the exposure of Mix17 to the cytosolic side of the membrane depends on its N-terminus.

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Resch, M., Frickel, J. S., Wen, R. C. S., Hell, K., Harner, M. E.. 2024-05-31. The N-terminus of mitochondrial Mix17 is exposed to the cytosol in an energy dependent manner. https://doi.org/10.1101/2024.05.30.596364

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