Loss of Mgr2P Destabilizes the TIM23 Channel and Reduces Mitochondrial Emission of Reactive Oxygen Species

Abstract

The TIM23 complex is a hub for translocation of preproteins into or across the mitochondrial inner membrane. This dual sorting mechanism is currently being investigated, and in yeast it seems to be regulated by a recently discovered subunit, the Mgr2 protein. Deletion of Mgr2p has been found to delay protein translocation into the matrix and accumulation in the inner membrane. This result and other findings suggested that Mgr2p controls the lateral release of inner membrane proteins harboring a stop-transfer signal that follows an N-terminal acid presequence. However, the mechanism of lateral release is unknown. Also unknown is whether the presence or absence of yeast Mgr2p might modulate reactive oxygen species (ROS), like its mammalian counterpart, Romo1. Here, we used patch clamp electrophysiology and spectrofluorimetry to investigate the effect of Mgr2p deletion upon the channel activity of TIM23 and upon emission of ROS from mitochondria. Our results suggest that Mgr2p deletion both destabilizes the TIM23 channel and decreases ROS emission. However, these two effects seem independent from each other, because ROS emission was not affected in the presence of presequence peptides.