UCP4, a novel brain‐specific mitochondrial protein that reduces membrane potential in mammalian cells

Mao, Weiguang; Yu, Xing; Zhong, Alan; Li, Wenlu; Brush, Jennifer; Sherwood, Sylvia; Adams, Sean H.; Pan, Guohua

doi:10.1016/s0014-5793(98)01713-x

Cited by 341 publications

(254 citation statements)

References 29 publications

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“…The present data indicate that UCP2, UCP3, StUCP and AtUCP alter the mitochondrial membrane potential recorded in i o in recombinant yeast and mammalian cells, and probably uncouple respiration [17,30,31,57,[59][60][61]84,85]. The respiration of isolated yeast mitochondria into which UCP2 had been introduced was less coupled than that of control mitochondria [30].…”

Section: Proton Transport Activity Of Ucp2 Ucp3 and Plant Ucps And mentioning

confidence: 57%

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The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP

Ricquier¹,

Bouillaud

2000

Biochemical Journal

614

115

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Animal and plant uncoupling protein (UCP) homologues form a subfamily of mitochondrial carriers that are evolutionarily related and possibly derived from a proton\anion transporter ancestor. The brown adipose tissue (BAT) UCP1 has a marked and strongly regulated uncoupling activity, essential to the maintenance of body temperature in small mammals. UCP homologues identified in plants are induced in a cold environment and may be involved in resistance to chilling. The biochemical activities and biological functions of the recently identified mammalian UCP2 and UCP3 are not well known. However, recent data support a role for these UCPs in State 4 respiration, respiration uncoupling and proton leaks in mitochondria. Moreover, genetic studies suggest that UCP2 and UCP3 play a part in

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Section: Proton Transport Activity Of Ucp2 Ucp3 and Plant Ucps And mentioning

confidence: 57%

“…In the case of UCP1, the localization in mitochondria was demonstrated by functional assays, immunodetection and purification. Moreover, the marked uncoupling activity of UCP1 overexpressed in yeast [7,81,82] [17].…”

Section: Mitochondrial Localization Of the Ucpsmentioning

confidence: 99%

The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP

Ricquier¹,

Bouillaud

2000

Biochemical Journal

614

115

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“…Since only hUCP2 was overexpressed in the brain (Figure 1d), and muscle hUCP3 mRNA expression greatly exceeded hUCP2 mRNA, the RCR data are consistent with increased mitochondrial uncoupling associated with the overexpression of human UCP2 and 3 genes as previously shown in vitro and in vivo. [1][2][3][4][5][6][7][8] Transgenic mice overexpressing UCP2 and 3 are lean We produced 12 independent lines of transgenic mice from the founding chimeras which were on a mixed strain background. The lines were maintained by backcrossing to C57BL/6J (B6).…”

Section: Effect Of Transgene Expression On Mitochondrial Uncouplingmentioning

confidence: 99%

“…All known uncoupling proteins (UCPs) influence the mitochondrial proton gradient, [1][2][3][4][5][6][7] but little is understood about the physiological consequences of UCP function (other than UCP1 in brown fat. 1,2,8 ) UCP2 is potentially the most interesting of these proteins because it is widely but variably expressed in many tissues including adipose, muscle, spleen, brain, and pituitary, 3,[9][10][11] and thus may influence many physiological processes.…”

Section: Introductionmentioning

confidence: 99%

Uncoupling proteins-2 and 3 influence obesity and inflammation in transgenic mice

et al. 2003

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OBJECTIVE:To test the hypothesis that either uncoupling protein-2 UCP2 or UCP3 or both together influence obesity and inflammation in transgenic mice. DESIGN: We generated 12 lines of transgenic mice for both human UCP2 and 3 using native promoters from a human bacterial artificial chromosome (BAC) clone. The BAC expresses no genes other than UCP2 and 3. Mice used for experiments are N4 or higher of backcross to C57BL/6J (B6). Each experiment used transgenic mice and their nontransgenic littermates. RESULTS: Northern blots confirmed expression on human UCP2 in adipose and spleen, while human UCP3 expression was detectable in gastrocnemius muscle. Western blots demonstrated a four-fold increase of UCP2 protein in spleens of Line 32 transgenic animals. Heterozygous mice of four lines showing expression of human UCP2 in spleen were examined for obesity phenotypes. There were no significant differences between Lines 1 and 32, but female transgenics of both lines had significantly smaller femoral fat depots than the control (littermate) mice (P ¼ 0.015 and 0.005, respectively). In addition, total fat of transgenic females was significantly less in Line 1 (P ¼ 0.05) and almost significantly different in Line 32 (P ¼ 0.06). Male Line 1 mice were leaner (P ¼ 0.04) while male Line 32 mice were almost significantly leaner (P ¼ 0.06). Heterozygous mice of Lines 35 and 44 showed no significant differences from the nontransgenic littermate controls. Effects of the UCP2/UCP3 transgene on obesity in Line 32 mice were confirmed by crossing transgenic mice with the B6.Cg-Ay agouti obese mice. B6.Cg-Ay carrying the UCP2/UCP3 transgene from Line 32 were significantly leaner than nontransgenic B6.Cg-Ay mice. Line 32 UCP2/UCP3 transgenics showed increased hypothalamic Neuropeptide (NPY) levels and food intake, with reduced spontaneous physical activity. Transgenic baseline interleukin4 (IL-4) and interleukin6 (IL-6) levels were low with lower or later increases after endotoxin injection compared to wild-type littermates. Endotoxin-induced fever was also diminished in transgenic male animals. Low-density lipoprotein (LDL) cholesterol levels were significantly higher in both Line 1 and 32 transgenics (P ¼ 0.05 and 0.001, respectively) after they had been placed on a moderate fat-defined diet containing 32% of calories from fat for 5 weeks. CONCLUSION: Moderate overexpression of UCP2 and 3 reduced fat mass and increased LDL cholesterol in two independent lines of transgenic mice. Thus, the reduced fat mass cannot be due to insertional mutagenesis since virtually identical fat pad weights and masses were observed with the two independent lines. Line 32 mice also have altered inflammation and mitochondrial function. We conclude that UCP2 and/or 3 have small but significant effects on obesity in mice, and that their mechanism of action may include alterations of metabolic rate.

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“…UCP4 and UCP5 share about 35-40% amino acid identity with UCP1-3. Mammalian UCP4 is exclusively expressed in different regions of the brain and spinal cord (Mao et al 1999;Smorodchenko et al 2009). UCP5 expression is highly enriched in the mammalian nervous system and is located exclusively in neurons (Sanchis et al 1998;Yu et al 2000;Kim-Han et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of uncoupling protein 4 in fat body and muscle mitochondria from the cockroach Gromphadorhina cocquereliana

Słocińska

Antos-Krzemińska

Rosiński

et al. 2011

J Bioenerg Biomembr

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We have identified and characterized an uncoupling protein in mitochondria isolated from leg muscle and from fat body, an insect analogue tissue of mammalian liver and adipose tissue, of the cockroach Gromphadorhina coquereliana (GcUCP). This is the first functional characterization of UCP activity in isolated insect mitochondria. Bioenergetic studies clearly indicate UCP function in both insect tissues. In resting (non-phosphorylating) mitochondria, cockroach GcUCP activity was stimulated by the addition of micromolar concentrations of palmitic acid and inhibited by the purine nucleotide GTP. Moreover, in phosphorylating mitochondria, GcUCP activity was able to divert energy from oxidative phosphorylation. Functional studies indicate a higher activity of GcUCP-mediated uncoupling in cockroach muscle mitochondria compared to fat body mitochondria. GcUCP activation by palmitic acid resulted in a decrease in superoxide anion production, suggesting that protection against mitochondrial oxidative stress may be a physiological role of UCPs in insects. GcUCP protein was immunodetected using antibodies raised against human UCP4 as a single band of around 36 kDa. GcUCP protein expression in cockroach muscle mitochondria was significantly higher compared to mitochondria isolated from fat body. LC-MS/MS analyses revealed 100% sequence identities for peptides obtained from GcUCP to UCP4 isoforms from D. melanogaster (the highest homology), human, rat or other insect mitochondria. Therefore, it can be proposed that cockroach GcUCP corresponds to the UCP4 isoforms of other animals.

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UCP4, a novel brain‐specific mitochondrial protein that reduces membrane potential in mammalian cells

Cited by 341 publications

References 29 publications

The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP

The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP

Uncoupling proteins-2 and 3 influence obesity and inflammation in transgenic mice

Identification and characterization of uncoupling protein 4 in fat body and muscle mitochondria from the cockroach Gromphadorhina cocquereliana

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