Abstract
Uncoupling protein-1 homologs are hypothesized to mediate mitochondrial proton leak. To test this hypothesis, we determined the effects of ATP and other nucleotides on liver and skeletal muscle mitochondrial non-phosphorylating respiration (VO2), membrane potential, FCCP-stimulated respiratory control ratios, and swelling. Neither ATP nor CTP affected liver or muscle proton leak, but both inhibited the respiratory chain. Unexpectedly, CMP stimulated liver proton leak (EC50~4.4±0.5 mM). Using CMP chromatography, we identified two proteins (M(r)=31.2 and 32.6 kDa) from liver mitochondria that are similar in size to members of the mitochondrial carrier protein family. We conclude (a) liver and muscle mitochondrial proton leak is insensitive to ATP and CTP, and (b) CMP activates a leak in liver mitochondria. The CMP-inducible leak may be mediated by a 30-32 kDa protein. Based on the high concentrations required, CMP is unlikely to be a physiologically important leak regulator. Nonetheless, our results show that tissues other than brown fat have inducible leaks that may be protein-mediated. Copyright (C) 2001 Elsevier Science B.V.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 314-328 |
| Number of pages | 15 |
| Journal | Biochimica et Biophysica Acta - Bioenergetics |
| Volume | 1503 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jan 19 2001 |
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Keywords
- Proton leak
- UCP2
- UCP3
- Uncoupling protein
ASJC Scopus subject areas
- Biophysics
Cite this
Nucleotide effects on liver and muscle mitochondrial non-phosphorylating respiration and membrane potential. / Jekabsons, Mika B.; Horwitz, Barbara A.
In: Biochimica et Biophysica Acta - Bioenergetics, Vol. 1503, No. 3, 19.01.2001, p. 314-328.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nucleotide effects on liver and muscle mitochondrial non-phosphorylating respiration and membrane potential
AU - Jekabsons, Mika B.
AU - Horwitz, Barbara A
PY - 2001/1/19
Y1 - 2001/1/19
N2 - Uncoupling protein-1 homologs are hypothesized to mediate mitochondrial proton leak. To test this hypothesis, we determined the effects of ATP and other nucleotides on liver and skeletal muscle mitochondrial non-phosphorylating respiration (VO2), membrane potential, FCCP-stimulated respiratory control ratios, and swelling. Neither ATP nor CTP affected liver or muscle proton leak, but both inhibited the respiratory chain. Unexpectedly, CMP stimulated liver proton leak (EC50~4.4±0.5 mM). Using CMP chromatography, we identified two proteins (M(r)=31.2 and 32.6 kDa) from liver mitochondria that are similar in size to members of the mitochondrial carrier protein family. We conclude (a) liver and muscle mitochondrial proton leak is insensitive to ATP and CTP, and (b) CMP activates a leak in liver mitochondria. The CMP-inducible leak may be mediated by a 30-32 kDa protein. Based on the high concentrations required, CMP is unlikely to be a physiologically important leak regulator. Nonetheless, our results show that tissues other than brown fat have inducible leaks that may be protein-mediated. Copyright (C) 2001 Elsevier Science B.V.
AB - Uncoupling protein-1 homologs are hypothesized to mediate mitochondrial proton leak. To test this hypothesis, we determined the effects of ATP and other nucleotides on liver and skeletal muscle mitochondrial non-phosphorylating respiration (VO2), membrane potential, FCCP-stimulated respiratory control ratios, and swelling. Neither ATP nor CTP affected liver or muscle proton leak, but both inhibited the respiratory chain. Unexpectedly, CMP stimulated liver proton leak (EC50~4.4±0.5 mM). Using CMP chromatography, we identified two proteins (M(r)=31.2 and 32.6 kDa) from liver mitochondria that are similar in size to members of the mitochondrial carrier protein family. We conclude (a) liver and muscle mitochondrial proton leak is insensitive to ATP and CTP, and (b) CMP activates a leak in liver mitochondria. The CMP-inducible leak may be mediated by a 30-32 kDa protein. Based on the high concentrations required, CMP is unlikely to be a physiologically important leak regulator. Nonetheless, our results show that tissues other than brown fat have inducible leaks that may be protein-mediated. Copyright (C) 2001 Elsevier Science B.V.
KW - Proton leak
KW - UCP2
KW - UCP3
KW - Uncoupling protein
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UR - http://www.scopus.com/inward/citedby.url?scp=0035910653&partnerID=8YFLogxK
U2 - 10.1016/S0005-2728(00)00209-7
DO - 10.1016/S0005-2728(00)00209-7
M3 - Article
C2 - 11115643
AN - SCOPUS:0035910653
VL - 1503
SP - 314
EP - 328
JO - Biochimica et Biophysica Acta - Bioenergetics
JF - Biochimica et Biophysica Acta - Bioenergetics
SN - 0005-2728
IS - 3
ER -