Lack of activation of UCP1 in isolated brown adipose tissue mitochondria by glucose-O-ω-modified saturated fatty acids of various chain lengths

Breen, Edmond J.; Pilgrim, Wayne; Clarke, Kieran; Yssel, Cristy; Farrell, Mark; Zhou, Jian; Murphy, Paul V.; Porter, Richard K.

doi:10.1007/s12154-013-0093-6

Cited by 4 publications

(2 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, FA molecules must be unipolar. Dicarboxylic FAs or FAs with bulky groups in the ω-end do not exhibit UCP uncoupling ( 48 , 202 , 203 ). Thus, the presence of UCP in biomembranes is not sufficient for uncoupling; also required are FAs able to flip-flop across the membrane and to be protonated and deprotonated.…”

Section: The Mechanism Of Uncoupling By the Ucpsmentioning

confidence: 99%

Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox SignalingReviewing Editors:Jerzy Beltowski, Joseph Burgoyne, Gabor Csanyi, Sergey Dikalov, Frank Krause, Anibal Vercesi, and Jeremy Ward

Ježek

Holendová

Garlid

et al. 2018

Antioxidants & Redox Signaling

109

View full text Add to dashboard Cite

Significance: Mitochondria are the energetic, metabolic, redox, and information signaling centers of the cell. Substrate pressure, mitochondrial network dynamics, and cristae morphology state are integrated by the protonmotive force Δp or its potential component, ΔΨ, which are attenuated by proton backflux into the matrix, termed uncoupling. The mitochondrial uncoupling proteins (UCP1–5) play an eminent role in the regulation of each of the mentioned aspects, being involved in numerous physiological events including redox signaling.Recent Advances: UCP2 structure, including purine nucleotide and fatty acid (FA) binding sites, strongly support the FA cycling mechanism: UCP2 expels FA anions, whereas uncoupling is achieved by the membrane backflux of protonated FA. Nascent FAs, cleaved by phospholipases, are preferential. The resulting Δp dissipation decreases superoxide formation dependent on Δp. UCP-mediated antioxidant protection and its impairment are expected to play a major role in cell physiology and pathology. Moreover, UCP2-mediated aspartate, oxaloacetate, and malate antiport with phosphate is expected to alter metabolism of cancer cells.Critical Issues: A wide range of UCP antioxidant effects and participations in redox signaling have been reported; however, mechanisms of UCP activation are still debated. Switching off/on the UCP2 protonophoretic function might serve as redox signaling either by employing/releasing the extra capacity of cell antioxidant systems or by directly increasing/decreasing mitochondrial superoxide sources. Rapid UCP2 degradation, FA levels, elevation of purine nucleotides, decreased Mg2+, or increased pyruvate accumulation may initiate UCP-mediated redox signaling.Future Directions: Issues such as UCP2 participation in glucose sensing, neuronal (synaptic) function, and immune cell activation should be elucidated. Antioxid. Redox Signal. 29, 667–714.

show abstract

Section: The Mechanism Of Uncoupling By the Ucpsmentioning

confidence: 99%

Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox SignalingReviewing Editors:Jerzy Beltowski, Joseph Burgoyne, Gabor Csanyi, Sergey Dikalov, Frank Krause, Anibal Vercesi, and Jeremy Ward

Ježek

Holendová

Garlid

et al. 2018

Antioxidants & Redox Signaling

109

View full text Add to dashboard Cite

show abstract

“…Crucial support for the FA cycling hypothesis comes from the observations of the inability of so-called "inactive FAs" (such as long chain dicarboxylic acids, FAs with bulky or polar groups at the ω end) to induce the protonophoric ability of UCP1 [56,59]. In contrast to the fatty acid cycling model, the protonophoric model postulates that the role of fatty acids is to insert into UCPs providing their α-carboxyls for proton conductance through UCPs [34,44].…”

Section: Fatty Acid Cycling Mechanismmentioning

confidence: 99%

Uncoupling mechanism and redox regulation of mitochondrial uncoupling protein 1 (UCP1)

Ježek

Jabůrek

Porter

2019

Biochimica et Biophysica Acta (BBA) - Bioenergetics

Self Cite

View full text Add to dashboard Cite

Brown adipose tissue (BAT) and brown in white (brite) adipose tissue, termed also beige adipose tissue, are major sites of mammalian nonshivering thermogenesis. Mitochondrial uncoupling protein 1 (UCP1), specific for these tissues, is the key factor for heat production. Recent molecular aspects of UCP1 structure provide support for the fatty acid cycling model of coupling, i.e. when UCP1 expels fatty acid anions in a uniport mode from the matrix, while uncoupling. Protonophoretic function is ensured by return of the protonated fatty acid to the matrix independent of UCP1. This mechanism is advantageous for mitochondrial uncoupling and compatible with heat production in a pro-thermogenic environment, such as BAT. It must still be verified whether posttranslational modification of UCP1, such as sulfenylation of Cys253, linked to redox activity, promotes UCP1 activity. BAT biogenesis and UCP1 expression, has also been linked to the pro-oxidant state of mitochondria, further endorsing a redox signalling link promoting an establishment of pro-thermogenic state. We discuss circumstances under which promotion of superoxide formation exceeds its attenuation by uncoupling in mitochondria and throughout point out areas of future research into UCP1 function.

show abstract

The conserved regulation of mitochondrial uncoupling proteins: From unicellular eukaryotes to mammals

Woyda-Płoszczyca

Jarmuszkiewicz

2017

Biochimica et Biophysica Acta (BBA) - Bioenergetics

View full text Add to dashboard Cite

Uncoupling proteins (UCPs) belong to the mitochondrial anion carrier protein family and mediate regulated proton leak across the inner mitochondrial membrane. Free fatty acids, aldehydes such as hydroxynonenal, and retinoids activate UCPs. However, there are some controversies about the effective action of retinoids and aldehydes alone; thus, only free fatty acids are commonly accepted positive effectors of UCPs. Purine nucleotides such as GTP inhibit UCP-mediated mitochondrial proton leak. In turn, membranous coenzyme Q may play a role as a redox state-dependent metabolic sensor that modulates the complete activation/inhibition of UCPs. Such regulation has been observed for UCPs in microorganisms, plant and animal UCP1 homologues, and UCP1 in mammalian brown adipose tissue. The origin of UCPs is still under debate, but UCP homologues have been identified in all systematic groups of eukaryotes. Despite the differing levels of amino acid/DNA sequence similarities, functional studies in unicellular and multicellular organisms, from amoebae to mammals, suggest that the mechanistic regulation of UCP activity is evolutionarily well conserved. This review focuses on the regulatory feedback loops of UCPs involving free fatty acids, aldehydes, retinoids, purine nucleotides, and coenzyme Q (particularly its reduction level), which may derive from the early stages of evolution as UCP first emerged.

show abstract

Lack of activation of UCP1 in isolated brown adipose tissue mitochondria by glucose-O-ω-modified saturated fatty acids of various chain lengths

Abstract: We previously demonstrated that

Cited by 4 publications

References 30 publications

Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox SignalingReviewing Editors:Jerzy Beltowski, Joseph Burgoyne, Gabor Csanyi, Sergey Dikalov, Frank Krause, Anibal Vercesi, and Jeremy Ward

Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox SignalingReviewing Editors:Jerzy Beltowski, Joseph Burgoyne, Gabor Csanyi, Sergey Dikalov, Frank Krause, Anibal Vercesi, and Jeremy Ward

Uncoupling mechanism and redox regulation of mitochondrial uncoupling protein 1 (UCP1)

The conserved regulation of mitochondrial uncoupling proteins: From unicellular eukaryotes to mammals

Contact Info

Product

Resources

About