Bcl-2 or Bcl-xL Overexpression Stimulates Lactic Fermentation without Affecting Whole Cell Respiration

Abstract

import complex TIM23 was just recently discovered: Mgr2. Our initial analysis of protein sequence showed that, like other TIM23 subunits, Mgr2 contained GXXXG motifs in certain trans membrane domains. These motifs were implicated in subunit oligomerization and pore stability. We hypothesized that Mgr2 was a structural component of the insertion pore, and that its deletion would impair peptide import and mitochondrial functioning. We analyzed protein import in Mgr2 deficient strains using fluorescein labeled synthetic import peptides. We also tested the effect of Mgr2 deletion on mitochondrial function by measuring accumulation of fluorescent membrane potential indicators and by determining respiratory activity using a Clark-type oxygen electrode. Moreover, TIM23 function was also examined in isolated mitochondria by patch clamp electrophysiology. The results suggested that Mgr2 depletion affected the basal membrane potential and the response to depolarizing and hyperpolarizing agents. Interestingly, patch clamp analysis suggested a decrease in pore size and gating properties. Further investigation will target the role of GXXXG motifs present in Mgr2 and other TIM23 components.