Difference between revisions of "Smith 2020 J Biol Chem"

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Smith CD, Schmidt CA, Lin CT, Fisher-Wellman KH, Neufer PD (2020) Flux through mitochondrial redox circuits linked to nicotinamide nucleotide transhydrogenase generates counterbalance changes in energy expenditure. J Biol Chem [Epub ahead of print].

» PMID: 32747443 Open Access

Smith Cody D, Schmidt Cameron A, Lin Chien-Te, Fisher-Wellman Kelsey H, Neufer P Darrell (2020) J Biol Chem

Abstract: Compensatory changes in energy expenditure occur in response to positive and negative energy balance, but the underlying mechanism remains unclear. Under low energy demand, the mitochondrial electron transport system (ETS) is particularly sensitive to added energy supply (i.e., reductive stress) which exponentially increases the rate of H₂O₂ (JH₂O₂) production. H₂O₂ is reduced to H₂O by electrons supplied by NADPH. NADP⁺ is reduced back to NADPH by activation of mitochondrial membrane potential-dependent nicotinamide nucleotide transhydrogenase (NNT). The coupling of reductive stress-induced JH₂O₂ production to NNT-linked redox buffering circuits provides a potential means of integrating energy balance with energy expenditure. To test this hypothesis, energy supply was manipulated by varying flux rate through β-oxidation in muscle mitochondria minus/plus pharmacological or genetic inhibition of redox buffering circuits. Here we show during both non-ADP and low-ADP stimulated respiration that accelerating flux through β-oxidation generates a corresponding increase in mitochondrial JH₂O₂ production, that the majority (∼70-80%) of H₂O₂ produced is reduced to H₂O by electrons drawn from redox buffering circuits supplied by NADPH, and that the rate of electron flux through redox buffering circuits is directly linked to changes in oxygen consumption mediated by NNT. These findings provide evidence that redox reactions within β-oxidation and the ETS serve as a barometer of substrate flux relative to demand, continuously adjusting JH₂O₂ production and, in turn, the rate at which energy is expended via NNT-mediated proton conductance. This variable flux through redox circuits provides a potential compensatory mechanism for fine-tuning energy expenditure to energy balance in real-time. • Keywords: Beta-oxidation, Bioenergetics, Electron transport system (ETS), Energy metabolism, Hydrogen sulfide, Mitochondrial metabolism, Nicotinamide nucleotide transhydrogenase, Redox regulation • Bioblast editor: Plangger M

Labels: MiParea: Respiration

Stress:Oxidative stress;RONS Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Isolated mitochondria

Regulation: mt-Membrane potential Coupling state: LEAK, OXPHOS, ET Pathway: F, N HRR: Oxygraph-2k, O2k-Fluorometer, TPP

2020-08, AmR

@@ Line 2: / Line 2: @@
 |title=Smith CD, Schmidt CA, Lin CT, Fisher-Wellman KH, Neufer PD (2020) Flux through mitochondrial redox circuits linked to nicotinamide nucleotide transhydrogenase generates counterbalance changes in energy expenditure. J Biol Chem [Epub ahead of print].
 |info=[https://www.ncbi.nlm.nih.gov/pubmed/32747443 PMID: 32747443 Open Access]
-|authors=Smith CD, Schmidt CA, Lin CT, Fisher-Wellman KH, Neufer PD
+|authors=Smith Cody D, Schmidt Cameron A, Lin Chien-Te, Fisher-Wellman Kelsey H, Neufer P Darrell
 |year=2020
 |journal=J Biol Chem
-|abstract=Compensatory changes in energy expenditure occur in response to positive and negative energy balance, but the underlying mechanism remains unclear. Under low energy demand, the mitochondrial electron transport system (ETS) is particularly sensitive to added energy supply (i.e., reductive stress) which exponentially increases the rate of H<sub>2</sub>O<sub>2</sub> (JH<sub>2</sub>O<sub>2</sub>) production. H<sub>2</sub>O<sub>2</sub> is reduced to H<sub>2</sub>O by electrons supplied by NADPH. NADP+ is reduced back to NADPH by activation of mitochondrial membrane potential-dependent nicotinamide nucleotide transhydrogenase (NNT). The coupling of reductive stress-induced JH<sub>2</sub>O<sub>2</sub> production to NNT-linked redox buffering circuits provides a potential means of integrating energy balance with energy expenditure. To test this hypothesis, energy supply was manipulated by varying flux rate through β-oxidation in muscle mitochondria minus/plus pharmacological or genetic inhibition of redox buffering circuits. Here we show during both non-ADP and low-ADP stimulated respiration that accelerating flux through β-oxidation generates a corresponding increase in mitochondrial JH<sub>2</sub>O<sub>2</sub> production, that the majority (∼70-80%) of H<sub>2</sub>O<sub>2</sub> produced is reduced to H<sub>2</sub>O by electrons drawn from redox buffering circuits supplied by NADPH, and that the rate of electron flux through redox buffering circuits is directly linked to changes in oxygen consumption mediated by NNT. These findings provide evidence that redox reactions within β-oxidation and the ETS serve as a barometer of substrate flux relative to demand, continuously adjusting JH<sub>2</sub>O<sub>2</sub> production and, in turn, the rate at which energy is expended via NNT-mediated proton conductance. This variable flux through redox circuits provides a potential compensatory mechanism for fine-tuning energy expenditure to energy balance in real-time.
+|abstract=Compensatory changes in energy expenditure occur in response to positive and negative energy balance, but the underlying mechanism remains unclear. Under low energy demand, the mitochondrial electron transport system (ETS) is particularly sensitive to added energy supply (i.e., reductive stress) which exponentially increases the rate of H<sub>2</sub>O<sub>2</sub> (JH<sub>2</sub>O<sub>2</sub>) production. H<sub>2</sub>O<sub>2</sub> is reduced to H<sub>2</sub>O by electrons supplied by NADPH. NADP<sup>+</sup> is reduced back to NADPH by activation of mitochondrial membrane potential-dependent nicotinamide nucleotide transhydrogenase (NNT). The coupling of reductive stress-induced JH<sub>2</sub>O<sub>2</sub> production to NNT-linked redox buffering circuits provides a potential means of integrating energy balance with energy expenditure. To test this hypothesis, energy supply was manipulated by varying flux rate through β-oxidation in muscle mitochondria minus/plus pharmacological or genetic inhibition of redox buffering circuits. Here we show during both non-ADP and low-ADP stimulated respiration that accelerating flux through β-oxidation generates a corresponding increase in mitochondrial JH<sub>2</sub>O<sub>2</sub> production, that the majority (∼70-80%) of H<sub>2</sub>O<sub>2</sub> produced is reduced to H<sub>2</sub>O by electrons drawn from redox buffering circuits supplied by NADPH, and that the rate of electron flux through redox buffering circuits is directly linked to changes in oxygen consumption mediated by NNT. These findings provide evidence that redox reactions within β-oxidation and the ETS serve as a barometer of substrate flux relative to demand, continuously adjusting JH<sub>2</sub>O<sub>2</sub> production and, in turn, the rate at which energy is expended via NNT-mediated proton conductance. This variable flux through redox circuits provides a potential compensatory mechanism for fine-tuning energy expenditure to energy balance in real-time.
 |keywords=Beta-oxidation, Bioenergetics, Electron transport system (ETS), Energy metabolism, Hydrogen sulfide, Mitochondrial metabolism, Nicotinamide nucleotide transhydrogenase, Redox regulation
 |editor=[[Plangger M]]
@@ Line 11: / Line 11: @@
 {{Labeling
 |area=Respiration
-|instruments=Oxygraph-2k
+|injuries=Oxidative stress;RONS
-|additional=2020-08
+|organism=Mouse
+|tissues=Skeletal muscle
+|preparations=Isolated mitochondria
+|topics=mt-Membrane potential
+|couplingstates=LEAK, OXPHOS, ET
+|pathways=F, N
+|instruments=Oxygraph-2k, O2k-Fluorometer, TPP
+|additional=2020-08, AmR
 }}