2005
DOI: 10.1042/bj20050890
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The basal proton conductance of mitochondria depends on adenine nucleotide translocase content

Abstract: The basal proton conductance of mitochondria causes mild uncoupling and may be an important contributor to metabolic rate. The molecular nature of the proton-conductance pathway is unknown. We show that the proton conductance of muscle mitochondria from mice in which isoform 1 of the adenine nucleotide translocase has been ablated is half that of wild-type controls. Overexpression of the adenine nucleotide translocase encoded by the stress-sensitive B gene in Drosophila mitochondria increases proton conductanc… Show more

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Cited by 342 publications
(303 citation statements)
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“…Mitochondrial uncoupling essentially drives an energy-dissipating proton cycle across the mitochondrial inner membrane resulting in a compensatory increase in O 2 consumption that is not accompanied by production of ATP [19]. This can be achieved through various mechanisms including activation of adenine nucleotide transporters (ANT) and uncoupling proteins (UCPs), which have been shown to be crucial for cell survival and homeostasis in various disease states [20][21][22][23][24]. Here we report that low micromolar concentrations of CO, delivered to isolated heart mitochondria by a water-soluble CO-RM, uncouple mitochondrial respiration consequently modulating both ROS production and bioenergetic parameters.…”
Section: Lo Iacono Et Almentioning
confidence: 99%
“…Mitochondrial uncoupling essentially drives an energy-dissipating proton cycle across the mitochondrial inner membrane resulting in a compensatory increase in O 2 consumption that is not accompanied by production of ATP [19]. This can be achieved through various mechanisms including activation of adenine nucleotide transporters (ANT) and uncoupling proteins (UCPs), which have been shown to be crucial for cell survival and homeostasis in various disease states [20][21][22][23][24]. Here we report that low micromolar concentrations of CO, delivered to isolated heart mitochondria by a water-soluble CO-RM, uncouple mitochondrial respiration consequently modulating both ROS production and bioenergetic parameters.…”
Section: Lo Iacono Et Almentioning
confidence: 99%
“…7 There has been no clear experimental evidence to date that differential ATP transport kinetics among the paralogs are critical for their specific roles in cells or tissues. Besides ATP transport activity, multiple studies indicate ANT paralogs may differ in their intramitochondrial sublocalization, 8 uncoupling activities, 9 binding partners 10 and effects on mitochondrial permeability transition pore (mPTP) opening and subsequent cellular survival and death control. 11 These intriguing subjects, however, have not been confirmed rigorously after the initial reports.…”
mentioning
confidence: 99%
“…To assess mitochondrial uncoupling (proton leak), respiration in the presence of oligomycin (enforced state 4) was used as a surrogate marker, as previously described (15,41,42). ANT1 knockdown caused a significant decrease in state 4 respiration (37 Ϯ 5 pmol/min in ANT1 siRNA versus 51 Ϯ 6 pmol/min in Ctrl siRNA, n ϭ 7, p ϭ 0.001), consistent with a role for ANT1 in basal proton leak (12). Furthermore, although the addition of LNO 2 caused a small but significant increase in state 4 respiration in control cells (51 Ϯ 6 pmol/min 3 61 Ϯ 9 pmol/min, n ϭ 7, p ϭ 0.02), LNO 2 was without effect in ANT1 siRNA cells (37 Ϯ 5 pmol/min 3 41 Ϯ 6 pmol/min, n ϭ 7, p ϭ 0.185) (supplemental Fig.…”
Section: Resultsmentioning
confidence: 99%
“…The composition of the PT pore is still a matter of debate, and whereas a role for cyclophilin D is well defined (6), opposing data exist regarding involvement of the adenine nucleotide translocase (ANT) (7,8). In addition to its potential role in the PT pore and cell death regulation (7,9,10), ANT plays essential roles in mitochondrial bioenergetics (10) and ANT1 (the major cardiac isoform (11)) is known to mediate a basal proton leak in mitochondria (12,13). Mild increases in mitochondrial proton leak (uncoupling) can confer protection against IR injury (14 -16), and this raises the possibility that ANT may play a role in cardioprotection.…”
mentioning
confidence: 99%