Uncoupling protein 1 controls reactive oxygen species in brown adipose tissue

Jastroch, Martin

doi:10.1073/pnas.1709064114

Cited by 43 publications

(28 citation statements)

References 30 publications

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“…Biomed Rev 29, 2018 Manoj, Gideon and Jacob the classical perception that free fatty acids were essential for UCP-mediated uncoupling (10)(11). In recent times, concrete physiological evidences have also accrued for a diffusible reactive oxygen species (DROS)-based origin for thermogenesis (12)(13)(14). In parallel, by comparing to the microsomal xenobiotic metabolism (mXM) model (15), we had discredited the long-standing explanations for mitochondrial oxidative phosphorylation (mOxPhos) and proposed a murburn scheme (a newly coined term standing for "mured/closed burning", connoting a mild but unrestricted redox catalysis) to explain mOxPhos (16)(17)(18).…”

Section: R E S E a R C H A R T I C L Ementioning

confidence: 99%

Murburn scheme for mitochondrial thermogenesis

Manoj¹,

Gideon²,

Jacob³

2018

Biomedical Reviews

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The physiology of thermogenesis in mitochondria (mediated by uncoupling protein, UCP) has traditionally been explained as the dissipation of proton gradient across the inner mitochondrial membrane into heat. However, there are differences of opinion ture. Recent experimental evidence suggests strong correlation of diffusible reactive oxygen species (DROS) with UCP-induced thermogenesis. Further, the mechanistic explanations of mitochondrial oxidative phosphorylation (mOxPhos) were recently revamped with murburn concept, which considers DROS as an obligatory catalytic agent in mOxPhos. Herein, we propose that of DROS. Thus, UCP facilitates DROS-reactions amongst themselves, forming water and liberating heat around the inner mitochondrial membrane. Thereby, the simple murburn scheme for biothermogenesis integrates structural information of UCP with its attributed physiological function.

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Section: R E S E a R C H A R T I C L Ementioning

confidence: 99%

Murburn scheme for mitochondrial thermogenesis

Manoj¹,

Gideon²,

Jacob³

2018

Biomedical Reviews

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“…Using mitochondria from brown adipose tissue of mice, Dlasková et al show that inhibition or ablation of UCP1 indeed increases both Δp and ROS formation, while Kazak et al demonstrate that such ablated mitochondria become dysfunctional by induction of ROS production via RET to Complex I . For UCP2, a well‐controlled study revealed induction of host UCP2 expression during Leishmania infection, lowering ROS generation in order to suppress macrophage defence mechanisms, and UCP2 also inhibited ROS‐mediated apoptosis in A549 cancer cells (during hypoxia) .…”

Section: Ros As a Mammalian Cell Signal: The Example Of Ucpsmentioning

confidence: 99%

Can All Major ROS Forming Sites of the Respiratory Chain Be Activated By High FADH₂/NADH Ratios?

Speijer

2018

BioEssays

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Aspects of peroxisome evolution, uncoupling, carnitine shuttles, supercomplex formation, and missing neuronal fatty acid oxidation (FAO) are linked to reactive oxygen species (ROS) formation in respiratory chains. Oxidation of substrates with high FADH 2 /NADH (F/N) ratios (e.g., FAs) initiate ROS formation in Complex I due to insufficient availability of its electron acceptor (Q) and reverse electron transport from QH 2 , e.g., during FAO or glycerol-3-phosphate shuttle use. Here it is proposed that the Q-cycle of Complex III contributes to enhanced ROS formation going from low F/N ratio substrates (glucose) to high F/N substrates. This contribution is twofold: 1) Complex III uses Q as substrate, thus also competing with Complex I; 2) Complex III itself will produce more ROS under these conditions. I link this scenario to the universally observed Complex III dimerization. The Q-cycle of Complex III thus again illustrates the tension between efficient ATP generation and endogenous ROS formation. This model can explain recent findings concerning succinate and ROS-induced uncoupling.

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“…This process protects against hypothermia and obesity . Moreover, UCP1 in BAT also contributes to decreased production of reactive oxygen species (ROS) by mitochondria . This is important in obesity, as there are increased circulating levels of glucose and lipids, steering excessive substrates into metabolic pathways, which in turn leads to increased ROS .…”

Section: Introductionmentioning

confidence: 99%

Eicosapentaenoic Acid Reduces Adiposity, Glucose Intolerance and Increases Oxygen Consumption Independently of Uncoupling Protein 1

Pahlavani

Ramalingam

Miller

et al. 2019

Molecular Nutrition Food Res

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Scope: Brown adipose tissue (BAT) dissipates energy through uncoupling protein 1 (UCP1) and has been proposed as an anti-obesity target. It was reported previously that a high-fat (HF) diet enriched in eicosapentaenoic acid (EPA) significantly increased UCP1 and other thermogenic markers in BAT. It is hypothesized that these effects are mediated through UCP1-dependent regulation. Methods and results: Wild-type (WT) and UCP1 knockout (KO) B6 male mice were housed at thermoneutrality and fed a HF diet, without or with eicosapentaenoic acid (EPA)-enriched fish oil. HF-fed KO mice were heavier and had higher BAT lipid content than other groups. Protective effects of EPA in WT, previously observed at 22°C (reduced adiposity, improved glucose tolerance, and increased UCP1), disappeared at thermoneutrality. Mitochondrial proteins, cytochrome c oxidase subunit 1 (COX I

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Uncoupling protein 1 controls reactive oxygen species in brown adipose tissue

Cited by 43 publications

References 30 publications

Murburn scheme for mitochondrial thermogenesis

Murburn scheme for mitochondrial thermogenesis

Can All Major ROS Forming Sites of the Respiratory Chain Be Activated By High FADH₂/NADH Ratios?

Eicosapentaenoic Acid Reduces Adiposity, Glucose Intolerance and Increases Oxygen Consumption Independently of Uncoupling Protein 1

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Uncoupling protein 1 controls reactive oxygen species in brown adipose tissue

Cited by 43 publications

References 30 publications

Murburn scheme for mitochondrial thermogenesis

Murburn scheme for mitochondrial thermogenesis

Can All Major ROS Forming Sites of the Respiratory Chain Be Activated By High FADH2/NADH Ratios?

Eicosapentaenoic Acid Reduces Adiposity, Glucose Intolerance and Increases Oxygen Consumption Independently of Uncoupling Protein 1

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Can All Major ROS Forming Sites of the Respiratory Chain Be Activated By High FADH₂/NADH Ratios?