Adenine nucleotide translocator promotes oxidative phosphorylation and mild uncoupling in mitochondria after dexamethasone treatment

Abstract

The composition of the mitochondrial inner membrane and uncoupling protein [such as adenine nucleotide translocator (ANT)] contents are the main factors involved in the energy-wasting proton leak. This leak is increased by glucocorticoid treatment under nonphosphorylating conditions. The aim of this study was to investigate mechanisms involved in glucocorticoid-induced proton leak and to evaluate the consequences in more physiological conditions (between states 4 and 3). Isolated liver mitochondria, obtained from dexamethasone-treated rats (1.5 mg.kg(-1).day(-1)), were studied by polarography, Western blotting, and high-performance thin-layer chromatography. We confirmed that dexamethasone treatment in rats induces a proton leak in state 4 that is associated with an increased ANT content, although without any change in membrane surface or lipid composition. Between states 4 and 3, dexamethasone stimulates ATP synthesis by increasing both the mitochondrial ANT and F1-F0 ATP synthase content. In conclusion, dexamethasone increases mitochondrial capacity to generate ATP by modifying ANT and ATP synthase. The side effect is an increased leak in nonphosphorylating conditions.

Expression of oxidative phosphorylation components in mitochondria of long-living Ames dwarf mice

“…mRNA levels are expressed as relative to wild-type mice the enhanced OXPHOS output in older dwarf mice. Other studies also suggest that glucocorticoids promote OXPHOS and enhance ATP synthesis via increases in ANT and ATP synthase (Arvier et al 2007). Ames dwarf mice exhibit significantly elevated plasma corticosteroid levels that may also contribute to the enhancement of the OXPHOS system observed in this study (Borg et al 1995).…”

Mitochondrial and sarcoplasmic reticulum abnormalities in cancer cachexia: Altered energetic efficiency?

“…Interestingly, there are four different ANT isoforms (ANT1, ANT2, ANT3 and ANT4) but ANT1 is the predominant isoform present in skeletal muscle and, although not normally included as a part of the OXPHOS system, it is a key protein regulating the mitochondrial ATP/ADP flux [36]. It seems that the activity of the transporter may be intimately linked to uncoupling of the respiratory chain, basically due to proton leakage across the inner mitochondrial membrane and, therefore, disruption of the electrochemical proton gradient that drives ATP synthesis in the mitochondria [37]. Interestingly, our results show an increased ANT1 gene expression in both GSN and EDL muscles during tumor growth (2.2 and 2-fold respectively), as shown in Table 1.…”

Mitochondrial proticity and ROS signaling: lessons from the uncoupling proteins

“…Adenine nucleotide translocase (ANT) and the uncoupling proteins (UCPs 1-3) represent the most well described proteins involved in proton leak [7,21]. Proton leak mechanisms involving ANT are not well understood; however, they have been shown to be quantitatively important, being responsible for upward of 50% of basal proton leak in some cells [22].…”