Mgr2 regulates membrane insertion of marginal stop‐transfer signals in the mitochondrial inner membrane

Abstract

The TIM23 complex mediates membrane insertion of presequence‐containing mitochondrial proteins via a stop‐transfer mechanism. Stop‐transfer signals consists of a hydrophobic transmembrane segments and flanking charges. Mgr2 functions as a lateral gatekeeper of the TIM23 complex. However, it remains elusive which features of stop‐transfer signals are discriminated by Mgr2. To determine the effects of Mgr2 on the TIM23‐mediated stop‐transfer pathway, we measured membrane insertion of model transmembrane segments of varied hydrophobicity and flanking charges in Mgr2 deletion or overexpression yeast strains. We found that upon deletion of Mgr2 the threshold hydrophobicity for membrane insertion or the requirement for matrix‐facing positive charges are reduced. These results imply that Mgr2‐mediated gatekeeper function is important to control membrane sorting of marginal stop‐transfer signals.Support or Funding InformationThis research was funded by grants from National Research Foundation of Korea (NRF‐2016R1A2B2013459) and Promising‐Pioneering Research Program through Seoul Nation University to HK. Work in the laboratory of MvdL is supported by the Deutsche Forschungsgemeinschaft (SFB 894, IRTG 1830). Work in the laboratory of RI is supported by the CNRS ATIP program.