Expression, Folding, and Proton Transport Activity of Human Uncoupling Protein-1 (UCP1) in Lipid Membranes

Hoang, Thu Trang; Smith, Matthew D.; Jelokhani-Niaraki, Masoud

doi:10.1074/jbc.m113.509935

Cited by 42 publications

(130 citation statements)

References 43 publications

(75 reference statements)

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“…Thus, the presence of UCP1 mRNA does not simply determine the uncoupling status, a matter already discussed by Nedergaard et al . Translation of UCP1 mRNA into UCP1 protein and UCP1 function is regulated by various factors such as epigenetic control and availability of substrates required for uncoupled respiration such as fatty acids, glucose and ADP . Thus, the differentiated MSCs apparently need an additional factor which might be present in BAT and WAT with BAT‐like properties upon cold exposure in vivo .…”

Section: Discussionmentioning

confidence: 95%

Women have more potential to induce browning of perirenal adipose tissue than men

Beukel

Grefhorst

Hoogduijn

et al. 2015

Obesity

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Objective: Brown adipose tissue (BAT) can generate heat by burning fatty acids, a process mediated by uncoupling protein 1 (UCP1). White adipose tissue (WAT) depots can gain BAT-like properties, and various studies have suggested that females have more active BAT or BAT-like WAT. We studied sex differences in BAT-like properties of human perirenal adipose tissue. Methods: Perirenal and subcutaneous adipose tissue was obtained from 20 male and 24 female healthy live kidney donors. Mesenchymal stem cells (MSCs), adipocyte precursor cells, were isolated from these depots to study whether intrinsic factors control BAT-like properties of the adipose tissue depots. Results: When average outside temperature a week before harvesting was below 118C, brown-like adipocytes expressing UCP1 were present in perirenal adipose tissue of women, but not of men. MSCs derived from perirenal adipose tissue expressed significantly more UCP1 when from female origin compared to male origin (P 5 0.009). However, UCP1 protein content and oxygen consumption rate did not differ between adipocytes derived from male and female perirenal MSCs. Conclusions: Female perirenal adipose tissue has a higher potency to gain BAT-like properties than male perirenal adipose tissue. The degree of gaining BAT-like properties depends on sex-specific intrinsic factors and environmental triggers such as temperature.

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Section: Discussionmentioning

confidence: 95%

Women have more potential to induce browning of perirenal adipose tissue than men

Beukel

Grefhorst

Hoogduijn

et al. 2015

Obesity

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“…This unusual electrochemical behavior of CL was associated with its participation in proton pumping across the membrane and important role in mitochondrial energy production [10]. Moreover, changing ionization of the CL molecule in the pH range where the physiological slightly basic (pH ~8) environment can undergo acidification (to pH ~7) immediately leads to many speculations on the significance of this transition in terms of possibly alternate interactions with a number of the IMM proteins, for example with mitochondrial uncoupling proteins [11]. Not surprisingly, significant efforts have been dedicated to refined measurements of the pK for CL’s phosphate groups.…”

Section: Introductionmentioning

confidence: 99%

Magic angle spinning 31P NMR spectroscopy reveals two essentially identical ionization states for the cardiolipin phosphates in phospholipid liposomes

Kooijman¹,

Swim²,

Graber³

et al. 2017

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Specific membrane lipid composition is crucial for optimized structural and functional organization of biological membranes. Cardiolipin is a unique phospholipid and important component of the inner mitochondrial membrane. It is involved in energy metabolism, inner mitochondrial membrane transport, regulation of multiple metabolic reactions and apoptotic cell death. The physico-chemical properties of cardiolipin have been studied extensively but despite all these efforts there is still lingering controversy regarding the ionization of the two phosphate groups of cardiolipin. Results obtained in the 1990s and early 2000s suggested that cardiolipin has two disparate pKa values where one of the protons was proposed to be stabilized by an intramolecular hydrogen bond. This has led to extensive speculations on the roles of these two putative ionization states of cardiolipin in mitochondria. More recently the notion of two pKa values has been challenged and rejected by several groups. These studies relied on external measurements of proton adsorption or electrophoretic mobility of membranes but did not take into account the low pH phase behavior and chemical stability of cardiolipin. Here we used 31P NMR to show that in the physiologically relevant membrane phospholipid environment, cardiolipin carries two negative charges at physiological pH. We additionally demonstrate the pH dependent phase behavior and chemical stability of cardiolipin containing membranes.

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“…The θ 208 / θ 222 ratio of the atTic20 spectrum in POPC vesicles is less than 1 (Figures 3 B and 4 B). Such low molar ellipiticity ratios between 208 and 222 nm have been used to signify coiled coil motifs or oligomerization of monomers and/or packing of helical domains within a monomer for other proteins [ 28 - 31 ]. We therefore used semi-native PAGE as a method to examine whether atTic20 reconstituted into liposomes displayed characteristics of an oligomeric protein.…”

Section: Resultsmentioning

confidence: 99%

Folding and self-association of atTic20 in lipid membranes: implications for understanding protein transport across the inner envelope membrane of chloroplasts

et al. 2014

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BackgroundThe Arabidopsis thaliana protein atTic20 is a key component of the protein import machinery at the inner envelope membrane of chloroplasts. As a component of the TIC complex, it is believed to form a preprotein-conducting channel across the inner membrane.ResultsWe report a method for producing large amounts of recombinant atTic20 using a codon-optimized strain of E. coli coupled with an autoinduction method of protein expression. This method resulted in the recombinant protein being directed to the bacterial membrane without the addition of a bacterial targeting sequence. Using biochemical and biophysical approaches, we were able to demonstrate that atTic20 homo-oligomerizes in vitro when solubilized in detergents or reconstituted into liposomes. Furthermore, we present evidence that the extramembranous N-terminus of the mature protein displays characteristics that are consistent with it being an intrinsically disordered protein domain.ConclusionOur work strengthens the hypothesis that atTic20 functions similarly to other small α-helical integral membrane proteins, such as Tim23, that are involved in protein transport across membranes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12858-014-0029-y) contains supplementary material, which is available to authorized users.

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Expression, Folding, and Proton Transport Activity of Human Uncoupling Protein-1 (UCP1) in Lipid Membranes

Cited by 42 publications

References 43 publications

Women have more potential to induce browning of perirenal adipose tissue than men

Women have more potential to induce browning of perirenal adipose tissue than men

Magic angle spinning 31P NMR spectroscopy reveals two essentially identical ionization states for the cardiolipin phosphates in phospholipid liposomes

Folding and self-association of atTic20 in lipid membranes: implications for understanding protein transport across the inner envelope membrane of chloroplasts

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