Fink 2019 FASEB J: Difference between revisions
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{{Publication | {{Publication | ||
|title=Fink BD, Yu L, Sivitz WI (2019) Modulation of complex II-energized respiration in muscle, heart, and brown adipose mitochondria by oxaloacetate and complex I electron flow. FASEB J | |title=Fink BD, Yu L, Sivitz WI (2019) Modulation of complex II-energized respiration in muscle, heart, and brown adipose mitochondria by oxaloacetate and complex I electron flow. FASEB J 33:11696-705. | ||
|info=[https://www.ncbi.nlm.nih.gov/pubmed/31361970 PMID: 31361970] | |info=[https://www.ncbi.nlm.nih.gov/pubmed/31361970 PMID: 31361970 Open Access] | ||
|authors=Fink BD, Yu L, Sivitz WI | |authors=Fink BD, Yu L, Sivitz WI | ||
|year=2019 | |year=2019 | ||
|journal=FASEB J | |journal=FASEB J | ||
|abstract=We recently reported that membrane potential (ฮฮจ) primarily determines the relationship of complex II-supported respiration by isolated skeletal muscle mitochondria to ADP concentrations. We observed that O2 flux peaked at low ADP concentration ([ADP]) (high ฮฮจ) before declining at higher [ADP] (low ฮฮจ). The decline resulted from oxaloacetate (OAA) accumulation and inhibition of succinate dehydrogenase. This prompted us to question the effect of incremental [ADP] on respiration in interscapular brown adipose tissue (IBAT) mitochondria, wherein ฮฮจ is intrinsically low because of uncoupling protein 1 (UCP1). We found that succinate-energized IBAT mitochondria, even in the absence of ADP, accumulate OAA and manifest limited respiration, similar to muscle mitochondria at high [ADP]. This could be prevented by guanosine 5'-diphosphate inhibition of UCP1. NAD+ cycling with NADH requires complex I electron flow and is needed to form OAA. Therefore, to assess the role of electron transit, we perturbed flow using a small molecule, N1-(3-acetamidophenyl)-N2-(2-(4-methyl-2-(p-tolyl)thiazol-5-yl)ethyl)oxalamide. We observed decreased OAA, increased NADH/NAD<sup>+</sup>, and increased succinate-supported mitochondrial respiration under conditions of low ฮฮจ (IBAT) but not high ฮฮจ (heart). In summary, complex II-energized respiration in IBAT mitochondria is tempered by complex I-derived OAA in a manner dependent on UCP1. These dynamics depend on electron transit in complex I. | |abstract=We recently reported that membrane potential (ฮฮจ) primarily determines the relationship of complex II-supported respiration by isolated skeletal muscle mitochondria to ADP concentrations. We observed that O2 flux peaked at low ADP concentration ([ADP]) (high ฮฮจ) before declining at higher [ADP] (low ฮฮจ). The decline resulted from oxaloacetate (OAA) accumulation and inhibition of succinate dehydrogenase. This prompted us to question the effect of incremental [ADP] on respiration in interscapular brown adipose tissue (IBAT) mitochondria, wherein ฮฮจ is intrinsically low because of uncoupling protein 1 (UCP1). We found that succinate-energized IBAT mitochondria, even in the absence of ADP, accumulate OAA and manifest limited respiration, similar to muscle mitochondria at high [ADP]. This could be prevented by guanosine 5'-diphosphate inhibition of UCP1. NAD<sup>+</sup> cycling with NADH requires complex I electron flow and is needed to form OAA. Therefore, to assess the role of electron transit, we perturbed flow using a small molecule, N1-(3-acetamidophenyl)-N2-(2-(4-methyl-2-(p-tolyl)thiazol-5-yl)ethyl)oxalamide. We observed decreased OAA, increased NADH/NAD<sup>+</sup>, and increased succinate-supported mitochondrial respiration under conditions of low ฮฮจ (IBAT) but not high ฮฮจ (heart). In summary, complex II-energized respiration in IBAT mitochondria is tempered by complex I-derived OAA in a manner dependent on UCP1. These dynamics depend on electron transit in complex I. | ||
|keywords=S1QEL 1.1, Brown adipose tissue, Mitochondrial respiratory chain, Succinate dehydrogenase | |keywords=S1QEL 1.1, Brown adipose tissue, Mitochondrial respiratory chain, Succinate dehydrogenase | ||
|editor=[[Plangger M]], | |editor=[[Plangger M]], | ||
|mipnetlab=US IA Iowa City Sivitz WI | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration | |area=Respiration | ||
|instruments=Oxygraph-2k | |organism=Mouse | ||
|additional= | |tissues=Heart, Skeletal muscle, Fat | ||
|preparations=Isolated mitochondria | |||
|enzymes=Uncoupling protein | |||
|topics=ADP, mt-Membrane potential | |||
|couplingstates=OXPHOS | |||
|pathways=N, S | |||
|instruments=Oxygraph-2k, TPP | |||
|additional=2019-08, | |||
}} | }} |
Latest revision as of 01:37, 3 April 2023
Fink BD, Yu L, Sivitz WI (2019) Modulation of complex II-energized respiration in muscle, heart, and brown adipose mitochondria by oxaloacetate and complex I electron flow. FASEB J 33:11696-705. |
Fink BD, Yu L, Sivitz WI (2019) FASEB J
Abstract: We recently reported that membrane potential (ฮฮจ) primarily determines the relationship of complex II-supported respiration by isolated skeletal muscle mitochondria to ADP concentrations. We observed that O2 flux peaked at low ADP concentration ([ADP]) (high ฮฮจ) before declining at higher [ADP] (low ฮฮจ). The decline resulted from oxaloacetate (OAA) accumulation and inhibition of succinate dehydrogenase. This prompted us to question the effect of incremental [ADP] on respiration in interscapular brown adipose tissue (IBAT) mitochondria, wherein ฮฮจ is intrinsically low because of uncoupling protein 1 (UCP1). We found that succinate-energized IBAT mitochondria, even in the absence of ADP, accumulate OAA and manifest limited respiration, similar to muscle mitochondria at high [ADP]. This could be prevented by guanosine 5'-diphosphate inhibition of UCP1. NAD+ cycling with NADH requires complex I electron flow and is needed to form OAA. Therefore, to assess the role of electron transit, we perturbed flow using a small molecule, N1-(3-acetamidophenyl)-N2-(2-(4-methyl-2-(p-tolyl)thiazol-5-yl)ethyl)oxalamide. We observed decreased OAA, increased NADH/NAD+, and increased succinate-supported mitochondrial respiration under conditions of low ฮฮจ (IBAT) but not high ฮฮจ (heart). In summary, complex II-energized respiration in IBAT mitochondria is tempered by complex I-derived OAA in a manner dependent on UCP1. These dynamics depend on electron transit in complex I. โข Keywords: S1QEL 1.1, Brown adipose tissue, Mitochondrial respiratory chain, Succinate dehydrogenase โข Bioblast editor: Plangger M โข O2k-Network Lab: US IA Iowa City Sivitz WI
Labels: MiParea: Respiration
Organism: Mouse
Tissue;cell: Heart, Skeletal muscle, Fat
Preparation: Isolated mitochondria
Enzyme: Uncoupling protein
Regulation: ADP, mt-Membrane potential
Coupling state: OXPHOS
Pathway: N, S
HRR: Oxygraph-2k, TPP
2019-08