scholarly journals Synergy of fatty acid and reactive alkenal activation of proton conductance through uncoupling protein 1 in mitochondria

2006 ◽  
Vol 395 (3) ◽  
pp. 619-628 ◽  
Author(s):  
Telma C. Esteves ◽  
Nadeene Parker ◽  
Martin D. Brand
Keyword(s):  
Proton Transport ◽  
Uncoupling Protein ◽  
Significant Activity ◽  
Proton Conductance ◽  
Uncoupling Protein 1 ◽  
Physiological Models ◽  
Synergistic Activation ◽  
Brown Adipose ◽  
The Individual ◽  
Kinetics Of

The kinetics of proton transport through mammalian UCP1 (uncoupling protein 1) expressed in yeast mitochondria were measured. There was little or no UCP1 activity in the absence of added palmitate, but significant activity in its presence. The activator 4-HNE (4-hydroxy-2-nonenal) had little effect when added alone, but significantly enhanced proton conductance in the presence of added palmitate. Activation of the proton conductance of UCP1 was synergistic: proton conductance in the presence of both palmitate and 4-HNE was significantly greater than the sum of the individual effects. Mitochondria from control yeast transformed with empty vector showed no such synergy, showing that synergy is a property of UCP1. Activation by the 4-HNE analogue trans-cinnamate showed essentially the same characteristics as activation by 4-HNE. Mitochondria from brown adipose tissue also showed synergistic activation of GDP-sensitive proton conductance by palmitate and 4-HNE. These results show that reactive alkenals activate the proton conductance of UCP1 more strongly when fatty acids are also added, with implications for both mechanistic and physiological models of UCP1 activation.

scholarly journals Ubiquinone is not required for proton conductance by uncoupling protein 1 in yeast mitochondria

2004 ◽  
Vol 379 (2) ◽  
pp. 309-315 ◽  
Author(s):  
Telma C. ESTEVES ◽  
Karim S. ECHTAY ◽  
Tanya JONASSEN ◽  
Catherine F. CLARKE ◽  
Martin D. BRAND
Keyword(s):  
Proton Transport ◽  
Uncoupling Protein ◽  
Coenzyme Q ◽  
Yeast Mitochondria ◽  
Proton Conductance ◽  
Wild Type ◽  
Uncoupling Protein 1 ◽  
Yeast Saccharomyces Cerevisiae ◽  
Mutant Strains ◽  
Wild Type Yeast

Q (coenzyme Q or ubiquinone) is reported to be a cofactor obligatory for proton transport by UCPs (uncoupling proteins) in liposomes [Echtay, Winkler and Klingenberg (2000) Nature (London) 408, 609–613] and for increasing the binding of the activator retinoic acid to UCP1 [Tomás, Ledesma and Rial (2002) FEBS Lett. 526, 63–65]. In the present study, yeast (Saccharomyces cerevisiae) mutant strains lacking Q and expressing UCP1 were used to determine whether Q was required for UCP function in mitochondria. Wild-type yeast strain and two mutant strains (CENΔCOQ3 and CENΔCOQ2), both not capable of synthesizing Q, were transformed with the mouse UCP1 gene. UCP1 activity was measured as fatty acid-dependent, GDP-sensitive proton conductance in mitochondria isolated from the cells. The activity of UCP1 was similar in both Q-containing and -deficient yeast mitochondria. We conclude that Q is neither an obligatory cofactor nor an activator of proton transport by UCP1 when it is expressed in yeast mitochondria.

A mitochondrial uncoupling artifact can be caused by expression of uncoupling protein 1 in yeast

2001 ◽  
Vol 356 (3) ◽  
pp. 779-789 ◽  
Author(s):  
Jeff A. STUART ◽  
James A. HARPER ◽  
Kevin M. BRINDLE ◽  
Mika B. JEKABSONS ◽  
Martin D. BRAND
Keyword(s):  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Physiological Property ◽  
Growth Defect ◽  
Yeast Mitochondria ◽  
Proton Conductance ◽  
Uncoupling Protein 1 ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Carrier ◽  
Brown Adipose

Uncoupling protein 1 (UCP1) from mouse was expressed in yeast and the specific (GDP-inhibitable) and artifactual (GDP-insensitive) effects on mitochondrial uncoupling were assessed. UCP1 provides a GDP-inhibitable model system to help interpret the uncoupling effects of high expression in yeast of other members of the mitochondrial carrier protein family, such as the UCP1homologues UCP2 and UCP3. Yeast expressing UCP1 at modest levels (approx. 1μg/mg of mitochondrial protein) showed no growth defect, normal rates of chemically uncoupled respiration and an increased non-phosphorylating proton conductance that was completely GDP-sensitive. The catalytic-centre activity of UCP1 in these yeast mitochondria was similar to that in mammalian brown-adipose-tissue mitochondria. However, yeast expressing UCP1 at higher levels (approx. 11μg/mg of mitochondrial protein) showed a growth defect. Their mitochondria had depressed chemically uncoupled respiration rates and an increased proton conductance that was partly GDP-insensitive. Thus, although UCP1 shows native behaviour at modest levels of expression in yeast, higher levels (or rates) of expression can lead to an uncoupling that is not a physiological property of the native protein and is therefore artifactual. This observation might be important in the interpretation of results from experiments in which the functions of UCP1homologues are verified by their ability to uncouple yeast mitochondria.

scholarly journals The Role of Uncoupling Protein 1 in the Metabolism and Adiposity of RIIβ-Protein Kinase A-Deficient Mice

2004 ◽  
Vol 18 (9) ◽  
pp. 2302-2311 ◽  
Author(s):  
Michael A. Nolan ◽  
Maria A. Sikorski ◽  
G. Stanley McKnight
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Uncoupling Protein ◽  
Mrna Level ◽  
Regulatory Subunit ◽  
Uncoupling Protein 1 ◽  
Brown Adipose ◽  
Kinase A

Abstract Mice lacking the RIIβ regulatory subunit of protein kinase A exhibit a 50% reduction in white adipose tissue stores compared with wild-type littermates and are resistant to diet-induced obesity. RIIβ−/− mice also have an increase in resting oxygen consumption along with a 4-fold increase in the brown adipose-specific mitochondrial uncoupling protein 1 (UCP1). In this study, we examined the basis for UCP1 induction and tested the hypothesis that the induced levels of UCP1 in RIIβ null mice are essential for the lean phenotype. The induction of UCP1 occurred at the protein but not the mRNA level and correlated with an increase in mitochondria in brown adipose tissue. Mice lacking both RIIβ and UCP1 (RIIβ−/−/Ucp1−/−) were created, and the key parameters of metabolism and body composition were studied. We discovered that RIIβ−/− mice exhibit nocturnal hyperactivity in addition to the increased oxygen consumption at rest. Disruption of UCP1 in RIIβ−/− mice reduced basal oxygen consumption but did not prevent the nocturnal hyperactivity. The double knockout animals also retained the lean phenotype of the RIIβ null mice, demonstrating that induction of UCP1 and increased resting oxygen consumption is not the cause of leanness in the RIIβ mutant mice.

scholarly journals Immunoreactivity of Canine Liposarcoma to Muscle and Brown Adipose Antigens

2017 ◽  
Vol 54 (6) ◽  
pp. 885-891 ◽  
Author(s):  
Elise E. B. LaDouceur ◽  
Sarah E. Stevens ◽  
Jason Wood ◽  
Christopher M. Reilly
Keyword(s):  
Uncoupling Protein ◽  
Smooth Muscle Actin ◽  
Antigen Expression ◽  
Muscle Actin ◽  
Uncoupling Protein 1 ◽  
Diagnostic Challenge ◽  
Brown Adipose ◽  
Well Differentiated ◽  
Relationship Of ◽  
Oil Red O

Liposarcoma, rhabdomyosarcoma, and hibernoma share some overlapping histologic and immunohistochemical features. Although immunohistochemistry (IHC) is commonly used in the diagnosis of these neoplasms, expression of muscle markers has been reported in human liposarcoma and canine hibernoma in addition to rhabdomyosarcoma. Thus, these neoplasms are a diagnostic challenge but important to distinguish because of differences in prognosis and treatment. Rhabdomyosarcoma and liposarcoma are both malignant, but rhabdomyosarcoma has a higher potential for metastasis. In contrast, hibernomas are benign with low risk of recurrence. This study investigated expression of the muscle markers desmin, myogenin, and α-smooth muscle actin (α-SMA) and the brown fat marker uncoupling protein 1 (UCP1) in 25 cases of canine liposarcoma using IHC. Oil red O histochemistry was performed to confirm the presence of lipid and the diagnosis of liposarcoma in cases that were not well-differentiated. The 25 cases included 15 well-differentiated, 5 pleomorphic, 3 myxoid, and 2 dedifferentiated subtypes of liposarcoma. By IHC, 23 of 25 expressed UCP1, 7 of 25 expressed α-SMA, 7 of 25 expressed desmin, and 3 of 25 expressed myogenin with no clear relationship of antigen expression and tumor subtype. These findings clarify the immunohistochemical profile of canine liposarcoma and suggest overlap in the expression of several muscle antigens and UCP1 between liposarcoma, hibernoma, and rhabdomyosarcoma.

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