Mode of membrane insertion of individual transmembrane segments in Mdl1 and Mdl2, multi-spanning mitochondrial ABC transporters

The sorting of an individual transmembrane (TM) segment of multi-spanning membrane proteins by the TIM23 complex in the mitochondrial inner membrane is poorly understood. Using the Mgm1 fusion approach, we attempted to assess the membrane insertion of individual TM segments of Mdl1p and Mdl2p, mitochondrial ABC transporters. Although these transporters share high sequence similarity, our results show that their membrane sorting patterns differ and that specific residues in TM domains strongly influence membrane insertion or translocation. These data imply that TIM23-mediated membrane insertion highly depends on the TM domain sequence context.