Mitochondrial performance in heat acclimation-a lesson from ischemia/reperfusion and calcium overload insults in the heart

作者：Assayag Miri; Saada Ann; Gerstenblith Gary; Canaana Haifa; Shlomai Rivka; Horowitz Michal^*

来源：American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2012, 303(8): R870-R881.

DOI：10.1152/ajpregu.00155.2012

• ATP production
• respiratory chain complex activity
• mitochondrial membrane potential
• mitochondrial Ca2+
• mitochondrial biogenesis

Assayag M, Saada A, Gerstenblith G, Canaana H, Shlomai R, Horowitz M. Mitochondrial performance in heat acclimation-a lesson from ischemia/reperfusion and calcium overload insults in the heart. Am J Physiol Regul Integr Comp Physiol 303: R870-R881, 2012. First published August 15, 2012; doi:10.1152/ajpregu.00155.2012.-Longterm heat acclimation (LTHA; 30 days, 34 degrees C) causes phenotypic adaptations that render protection against ischemic/reperfusion insult (I/R, 30 min global ischemia and 40 min reperfusion) via heat acclimation-mediated cross-tolerance (HACT) mechanisms. Shortterm acclimation (STHA, 2 days, 34 degrees C), in contrast, is characterized by cellular perturbations, leading to increased susceptibility to insults. Here, we tested the hypothesis that enhanced mitochondrial respiratory function is part of the acclimatory repertoire and that the 30-day regimen is required for protection via HACT. We subjected isolated hearts and mitochondria from controls (C), STHA, or LTHA rats to I/R, hypoxia/reoxygenation, or Ca2+ overload insults. Mitochondrial function was assessed by measuring O-2 consumption, membrane potential (Delta Psi m), mitochondrial Ca2+ ([Ca2+]m), ATP production, respiratory chain complex activities, and molecular markers of mitochondrial biogenesis. Our results, combining physiological and biochemical parameters, confirmed that mitochondria from LTHA rats subjected to insults, in contrast to C, preserve respiratory functions (e.g., upon I/R, C mitochondria fueled by glutamate-malate, demonstrated decreases of 81%, 13%, 25%, and 50% in O-2/P ratio, ATP production, Delta Psi m, and complex I activity, respectively, whereas the corresponding LTHA parameters remained unchanged). STHA mitochondria maintained Delta Psi m but did not preserve ATP production. LTHA [Ca2+]m was significantly higher than that of C and STHA and was not affected by the hypoxia/reoxygenation protocol compared with C. Enhanced mitochondrial biogenesis markers, switched-on during STHA coincidentally with enhanced membrane integrity (Delta Psi m), were insufficient to confer intact respiratory function upon insult. LTHA was required for respiratory complex I adaptation and HACT. Stabilized higher basal [Ca2+]m and attenuated Ca2+ overload are likely connected to this adaptation.

• 出版日期2012-10