An alternative function for human uncoupling protein 3: protection of mitochondria against accumulation of nonesterified fatty acids inside the mitochondrial matrix
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ABSTRACT The physiological function of the human uncoupling protein 3 UCP3, which was discovered in 1997, is unknown. Here we evaluate the available data on human UCP3 expression and show that UCP3 is up‐regulated in situations where fatty acid delivery to the mitochondria exceeds oxidative capacity, whereas down‐regulation of UCP3 is observed when oxidative capacity is enhanced. With a surplus of fatty acid delivery, accumulation of nonesterified fatty acids in the cytoplasm is likely to occur. Although the inner mitochondrial membrane provides a barrier for nones‐terified fatty acids, neutral nonesterified fatty acids can partition into the phospholipid bilayer and flip‐flop to the other side of the membrane, where they can be released into the mitochondrial matrix. Due to pH differences, these nonesterified fatty acids will be pro‐tonated. Because fatty acid anions can neither be metabolized inside the matrix or cross the inner mito‐chondrial membrane, accumulation of nonesterified fatty acids inside the matrix might occur. Therefore, we postulate that UCP3 is required for the outward translocation of fatty acids from the mitochondrial matrix. In this way, UCP3 is involved in the protection of mitochondria against accumulation of nonesterified fatty acids inside the mitochondrial matrix.—Schrauwen, P., Saris, W. H. M., Hesselink, M. K. C. An alternative function for human uncoupling protein 3: protection of mitochondria against accumulation of nonesterified fatty acids inside the mitochondrial matrix. FASEB J . 15, 2497–2502 (2001)
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Self-citationUncoupling Proteins: Role in Insulin Resistance and Insulin Insufficiency
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Self-citationSchrauwen, P., & Hesselink, M. K. C. (2003) · Proceedings of The Nutrition Society · doi:10.1079/pns2003277 · Cited by 66 · see citing works
Self-citationMitochondrial uncoupling protein 3 and its role in cardiac- and skeletal muscle metabolism
Nabben, M., & Joris Hoeks, J. (2007) · Physiology & Behavior · doi:10.1016/j.physbeh.2007.11.039 · Cited by 65 · see citing works
Long-term high-fat feeding induces greater fat storage in mice lacking UCP3
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Baicalin reduces mitochondrial damage in streptozotocin‐induced diabetic Wistar rats
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Anticancer Properties of PPARα‐Effects on Cellular Metabolism and Inflammation
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Rapid turnover of mitochondrial uncoupling protein 3
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Cha, S. H., Hu, Z., & Lane, M. D. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.03.026 · Cited by 56 · see citing works
Beneficial Effects of Exercise on Muscle Mitochondrial Function in Diabetes Mellitus
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Self-citationMechanisms of statin‐induced new‐onset diabetes
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Čater, M., & Bombek, L. K. (2022) · Antioxidants · doi:10.3390/antiox11081473 · Cited by 51 · see citing works
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Role of UCP3 in state 4 respiration during contractile activity-induced mitochondrial biogenesis
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The energetic implications of uncoupling protein-3 in skeletal muscle
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Joris Hoeks, J., Hesselink, M. K. C., van Bilsen, M., Schaart, G., Vusse, G. J., Saris, W. H. M., & Schrauwen, P. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)01343-7 · Cited by 44 · see citing works
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Tunstall, R. J., Mehan, K. A., Hargreaves, M., Spriet, L. L., & Cameron-Smith, D. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)00473-4 · Cited by 42 · see citing works
Uncoupling Protein-3 Content Is Decreased in Peripheral Skeletal Muscle of Patients with COPD
Gosker, H. R., Schrauwen, P., Hesselink, M. K. C., Schaart, G., van der Vusse, G. J., Wouters, E. F. M., & Schols, A. M. W. J. (2003) · European Respiratory Journal · doi:10.1183/09031936.03.00089802 · Cited by 42 · see citing works
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Role of lipid-derived mediators in skeletal muscle insulin resistance
Taube, A., Eckardt, K., & Eckel, J. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00241.2009 · Cited by 40 · see citing works
Gene expression profiling in livers of mice after acute inhibition of β-oxidation
van der Leij, F. R., Bloks, V. W., Grefhorst, A., Hoekstra, J., Gerding, A., Kooi, K. A., Gerbens, F., Meerman, G. T., & Kuipers, F. (2007) · Genomics · doi:10.1016/j.ygeno.2007.08.004 · Cited by 40 · see citing works
Mostyn, A., Litten, J. C., Perkins, K. S., Euden, P. J., Corson, A. M., Symonds, M. E., & Clarke, L. (2005) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00423.2004 · Cited by 40 · see citing works
Nabben, M., Shabalina, I. G., Moonen‐Kornips, E., van Beurden, D., Cannon, B., Schrauwen, P., Nedergaard, J., & Joris Hoeks, J. (2011) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2011.04.003 · Cited by 39 · see citing works
Self-citationMingrone, G., Rosa, G., Greco, A. V., Manco, M., Véga, N., Hesselink, M. K. C., Castagneto, M., Schrauwen, P., & Vidal, H. (2003) · Obesity Research · doi:10.1038/oby.2003.91 · Cited by 38 · see citing works
Self-citationMayrhofer, C., Krieger, S., Huttary, N., Chang, M. W.-F., Grillari, J., Allmaier, G. M., & Kerjaschki, D. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.080654 · Cited by 36 · see citing works
Nukitrangsan, N., Okabe, T., Toda, T., Inafuku, M., Iwasaki, H., & Oku, H. (2012) · Journal of Oleo Science · doi:10.5650/jos.61.89 · Cited by 34 · see citing works
Involvement of UCP3 in mild uncoupling and lipotoxicity
Joris Hoeks, J., Hesselink, M. K. C., & Schrauwen, P. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2006.02.005 · Cited by 34 · see citing works
Self-citationRole of UCP2 and UCP3 in nutrition and obesity
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Russell, A. P., Schrauwen, P., Somm, E., Gastaldi, G., Hesselink, M. K. C., Schaart, G., Moonen‐Kornips, E., Lo, S. K., Bufano, D., Giacobino, J., et al. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030885 · Cited by 31 · see citing works
Self-citationSchrauwen, P. (2002) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-200205000-00005 · Cited by 30 · see citing works
Self-citationSilvestri, E., Moreno, M., Lombardi, A., Ragni, M., de Lange, P., Alexson, S. E. H., Lanni, A., & Goglia, F. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.02.022 · Cited by 29 · see citing works
The effect of mild cold exposure on UCP3 mRNA expression and UCP3 protein content in humans
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Self-citationEffect of Lipid Infusion on Metabolism and Force of Rat Skeletal Muscles During Intense Contractions
Silveira, L. R., Hirabara, S. M., Alberici, L. C., Lambertucci, R. H., Peres, C. M., Takahashi, H., Pettri, A., Alba‐Loureiro, T. C., Luchessi, A. D., Cury‐Boaventura, M. F., et al. (2007) · Cellular Physiology and Biochemistry · doi:10.1159/000104168 · Cited by 28 · see citing works
Effect of 2 weeks of endurance training on uncoupling protein 3 content in untrained human subjects
Schrauwen, P., Russell, A. P., Moonen‐Kornips, E., Boon, N., & Hesselink, M. K. C. (2005) · Acta Physiologica Scandinavica · doi:10.1111/j.1365-201x.2004.01393.x · Cited by 28 · see citing works
Self-citationVariation in the uncoupling protein 2 and 3 genes and human performance
Dhamrait, S. S., Williams, A. G., Day, S. H., Skipworth, J. R. A., Payne, J. R., WORLD, M. J., Humphries, S. E., & Montgomery, H. (2012) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00766.2011 · Cited by 27 · see citing works
MicroRNA-152 Promotes Slow-Twitch Myofiber Formation via Targeting Uncoupling Protein-3 Gene
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Reptilian uncoupling protein: functionality and expression in sub-zero temperatures
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Uncoupling protein‐3 sensitizes cells to mitochondrial‐dependent stimulus of apoptosis
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Eat and Death: Chronic Over-Eating
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Muscle-UCP3 in the regulation of energy metabolism
Guardia, L. D., Luzi, L., & Codella, R. (2024) · Mitochondrion · doi:10.1016/j.mito.2024.101872 · Cited by 22 · see citing works
- Authors
- SCHRAUWEN, P., SARIS, W. H. M., & HESSELINK, M. K. C.
- Affiliations
- Maastricht University (NL)
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2001-11
- Volume
- 15
- Issue
- 13
- Pages
- 2497-2502
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W1969876145
- Cited by
- 172
- References
- 47
- Citations by year
- 2024: 2 · 2023: 2 · 2022: 4 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 5 · 2015: 2 · 2014: 6 · 2013: 5 · 2012: 4
- FWCI
- 5.47
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- UCP3, free fatty acids, mitochondrial matrix, fatty acid translocation, mitochondrial membrane, oxidative capacity, mitochondrial protection
- MeSH terms
- Uncoupling Protein 3, Animals, Biological Transport, Carrier Proteins, Fatty Acids, Nonesterified, Humans, Intracellular Membranes, Ion Channels, Mitochondria, Models, Biological, Mitochondrial Proteins
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