Cited by 968Adipose Tissue and MetabolismMitochondrial Function and PathologyATP Synthase and ATPases Research

Mechanism of Fatty-Acid-Dependent UCP1 Uncoupling in Brown Fat Mitochondria

Open access
Fedorenko, Andriy, Lishko, Polina V., Kirichok, Yuriy·2012·Cell

Abstract

Mitochondrial uncoupling protein 1 (UCP1) is responsible for nonshivering thermogenesis in brown adipose tissue (BAT). Upon activation by long-chain fatty acids (LCFAs), UCP1 increases the conductance of the inner mitochondrial membrane (IMM) to make BAT mitochondria generate heat rather than ATP. Despite being a member of the family of mitochondrial anion carriers (SLC25), UCP1 is believed to transport H(+) by an unusual mechanism that has long remained unresolved. Here, we achieved direct patch-clamp measurements of UCP1 currents from the IMM of BAT mitochondria. We show that UCP1 is an LCFA anion/H(+) symporter. However, the LCFA anions cannot dissociate from UCP1 due to hydrophobic interactions established by their hydrophobic tails, and UCP1 effectively operates as an H(+) carrier activated by LCFA. A similar LCFA-dependent mechanism of transmembrane H(+) transport may be employed by other SLC25 members and be responsible for mitochondrial uncoupling and regulation of metabolic efficiency in various tissues.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.cell.2012.09.010

Cites

47 of 47 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Free fatty acids resulting from lipolysis are used both as energy substrates and as activators of UCP1 to uncouple ATP production from mitochondrial respiration into heat.

    “Free fatty acids, resulting from lipolysis, are used both as energy substrates and as activators of UCP1 to uncouple ATP production from mitochondrial respiration into heat 73, 85.”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Bruce PY 2001 Organic Chemistry Upper Saddle River, NJ Pearson Education

Cited by

Sorted by citations

Authors
Fedorenko, A., Lishko, P. V., & Kirichok, Y.
Affiliations
University of California, San Francisco (US)
Corresponding author
Kirichok, Yuriy
Venue
Cell
Publisher
Elsevier BV
Published
2012-10
Volume
151
Issue
2
Pages
400-413
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2047306805
Cited by
968
References
47
Citations by year
2026: 47 · 2025: 79 · 2024: 88 · 2023: 89 · 2022: 92 · 2021: 88 · 2020: 101 · 2019: 76 · 2018: 66 · 2017: 67 · 2016: 56 · 2015: 56 · 2014: 41 · 2013: 20
FWCI
25.08
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Larry L. Hillblom Foundation
  • National Institutes of Health (1dp2od004656-01)
  • University of California, San Francisco
Topics
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
Keywords
UCP1, brown adipose tissue, long-chain fatty acids, mitochondrial uncoupling, non-shivering thermogenesis, proton transport, hydrophobic interactions, inner mitochondrial membrane
MeSH terms
Uncoupling Protein 1, Animals, Binding Sites, Adipose Tissue, Brown, Cytoplasm, Fatty Acids, Ion Channels, Protons, Purines, Patch-Clamp Techniques, Mitochondrial Proteins, Mitochondrial Membranes, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review