Cited by 174Mitochondrial Function and PathologyAdipose Tissue and MetabolismMetabolism and Genetic Disorders

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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SCHRAUWEN, PATRICK, SARIS, WIM H. M., HESSELINK, MATTHIJS K C.·2001·The FASEB Journal

Abstract

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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Crossref · 10.1096/fj.01-0400hyp

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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
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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