Resistance to Ca~(2+)-induced opening of the permeability transition pore differs in mitochondria from glycolytic and oxidative muscles

摘要

First published May 21, 2008; doi:10.1152/ajpregu.90357.2008-This study determined whether susceptibility to opening of the permeability transition pore (FTP) varies according to muscle phenotype represented by the slow oxidative soleus (Sol) and superficial white gastrocnemius (WG). Threshold for Ca~(2+)-induced mitochondrial Ca~(2+) release following PTP opening was determined with a novel approach using permeabilized ghost myofibers. Threshold values for PTP opening were approximately threefold higher in fibers from WG compared with those from Sol (124 +- 47 vs. 30.4 +- 6.8 pmol Ca~(2+)/mU citrate synthase). A similar phenomenon was also observed in isolated mitochondria (threshold: 121 +- 60 vs. 40 +- 10 nmol Ca~(2+)/mg protein in WG and Sol), indicating that this was linked to differences in mitochondrial factors between the two muscles. The resistance of WG fibers to PTP opening was not related to the expression of putative protein modulators (cyclophilin D, adenylate nucleotide translocator-1, and voltage-dependent anion channels) or to difference in respiratory properties and occurred despite the fact that production of reactive oxygen species, which promote pore opening, was higher than in the Sol. However, endogenous matrix Ca~(2+) measured in mitochondria isolated under resting baseline conditions was approximately twofold lower in the WG than in the Sol (56 +- 4 vs. 1ll +- 11 nmol/mg protein), which significantly accounted for the resistance of WG. Together, these results reveal fiber type differences in the sensitivity to Ca~(2+)-induced PTP opening, which may constitute a physiological mechanism to adapt mitochondria to the differences in Ca~(2+) dynamics between fiber types.