Polyunsaturated fatty acids activate human uncoupling proteins 1 and 2 in planar lipid bilayers.
Uncoupling proteins 1 (UCP1) and 2 (UCP2) belong to the family of mitochondrial anion transporters and share 59% sequence identity with each other. Whereas UCP1 was shown to be responsible for the rapid production of heat in brown adipose tissue, the primary function and transport properties of ubiquitously expressed UCP2 are controversially discussed. Here, for the first time, the activation pattern of the recombinant human UCP2 in comparison to the recombinant human UCP1 are studied using a well-defined system of planar lipid bilayers. It is shown that despite apparently different physiological functions, hUCP2 exhibited its protonophoric function similar to hUCP1--exclusively in the presence of long-chain fatty acids (FA). The calculated hUCP2 transport rate of 4.5 s(-1) is the same order of magnitude, as shown previously for UCP1. It leads to the conclusion that the differences in the activity of both proteins in living mitochondria are based exclusively on their different expression level. Both proteins are activated much more effectively by polyunsaturated than by saturated FA. The proton and total membrane conductances increased in the range palmitic < oleic < eicosatrienoic < linoleic < retinoic < arachidonic acids. The higher uncoupling protein (UCP)-dependent conductance in the presence of polyunsaturated FA is explained on the basis of the FA cycling hypothesis.
Beck
Valeri
V
Institute of Cell Biology and Neurobiology, Charité Universitätsmedizin, Charitéplatz 1, 10117 Berlin, Germany.
Jabůrek
Martin
M
Demina
Tatiana
T
Rupprecht
Anne
A
Porter
Richard K
RK
Jezek
Petr
P
Pohl
Elena E
EE
D000838:Anions; D005231:Fatty Acids, Unsaturated / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000737:chemistry; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008954:Models, Biological; D009711:Nucleotides / Q000737:chemistry; D011522:Protons; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins / Q000737:chemistry; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2
D000838:Anions; D005231:Fatty Acids, Unsaturated; D007473:Ion Channels; D008051:Lipid Bilayers; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D009711:Nucleotides; D011522:Protons; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; C000604371:UCP1 protein, human; C000604389:UCP2 protein, human; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2