Schrauwen Patrick, Hoeks Joris, Schaart Gert, Kornips Esther, Binas Bert, Van De Vusse Ger J, Van Bilsen Marc, Luiken Joost J F P, Coort Susan L M, Glatz Jan F C, Saris Wim H M, Hesselink Matthijs K C
Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht , Maastricht University, The Netherlands.
FASEB J. 2003 Dec;17(15):2272-4. doi: 10.1096/fj.03-0515fje. Epub 2003 Oct 2.
In contrast to UCP1, the primary function of UCP3 is not the dissipation of energy. Rather, several lines of evidence suggest that UCP3 is related to cellular long-chain fatty acid homeostasis. If long-chain fatty acids enter the mitochondrial matrix in their non-esterified form, they cannot be metabolized and may exert deleterious effects. To test the feasibility that UCP3 exports fatty acid anions, we systematically interfered at distinct steps in the fatty acid metabolism pathway, thereby creating conditions in which the entry of (non-esterified) fatty acids into the mitochondrial matrix is enhanced. First, reducing the cellular fatty acid binding capacity, known to increase cytosolic concentrations of non-esterified fatty acids, up-regulated UCP3 5.3-fold. Second, inhibition of mitochondrial entry of esterified long-chain fatty acids up-regulated UCP3 by 1.9-fold. Third, high-fat diets, to increase mitochondrial supply of non-esterified long-chain fatty acids exceeding oxidative capacity, up-regulated UCP3 twofold. However, feeding a similar amount of medium-chain fatty acids, which can be oxidized inside the mitochondrial matrix and therefore do not need to be exported from the matrix, did not affect UCP3 protein levels. These data are compatible with a physiological function of UCP3 in facilitating outward transport of long-chain fatty acid anions, which cannot be oxidized, from the mitochondrial matrix.
与解偶联蛋白1（UCP1）不同，解偶联蛋白3（UCP3）的主要功能并非能量耗散。相反，多条证据表明UCP3与细胞内长链脂肪酸稳态有关。如果长链脂肪酸以非酯化形式进入线粒体基质，它们将无法被代谢，并可能产生有害影响。为了测试UCP3输出脂肪酸阴离子的可行性，我们在脂肪酸代谢途径的不同步骤进行了系统性干预，从而创造出增强（非酯化）脂肪酸进入线粒体基质的条件。首先，降低细胞脂肪酸结合能力（已知这会增加非酯化脂肪酸的胞质浓度），使UCP3上调了5.3倍。其次，抑制酯化长链脂肪酸进入线粒体使UCP3上调了1.9倍。第三，高脂饮食会增加非酯化长链脂肪酸的线粒体供应，使其超过氧化能力，从而使UCP3上调了两倍。然而，喂食等量的中链脂肪酸（其可在线粒体基质内被氧化，因此无需从基质输出）对UCP3蛋白水平没有影响。这些数据与UCP3在促进无法被氧化的长链脂肪酸阴离子从线粒体基质向外转运方面的生理功能相符。
