Natural and Azido Fatty Acids Inhibit Phosphate Transport and Activate Fatty Acid Anion Uniport Mediated by the Mitochondrial Phosphate Carrier

Engstová, Hana; Žáčková, Markéta; Růžička, Michal; Meinhardt, Andrea; Hanuš, Jan; Krämer, Reinhard; Ježek, Petr

doi:10.1074/jbc.m009409200

Cited by 18 publications

(8 citation statements)

References 44 publications

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“…The resulting FA-induced H ϩ efflux increased with increasing initial amount of W303 yeast mitochondria. It is likely mediated by yeast carriers of the HTP flow-through, such as the ADP/ ATP carrier (48) or the phosphate carrier (39,49). In turn, the ATP insensitivity of H ϩ efflux with the reconstituted W303 extract and only slight (Ͻ10%) inhibition of FA-induced H ϩ efflux in UCP2 or UCP3 proteoliposomes by CAT agaric acid, 3 or methylenediphosphonate suggest that the ATP-sensitive H ϩ fluxes in UCP2 (UCP3) proteoliposomes are indeed due to UCP2 (UCP3) function, respectively.…”

Section: Fig 1 (A and B) Illustrates The Inhibition Of The Lauric Acmentioning

confidence: 99%

Activating ω-6 Polyunsaturated Fatty Acids and Inhibitory Purine Nucleotides Are High Affinity Ligands for Novel Mitochondrial Uncoupling Proteins UCP2 and UCP3

Žáčková

Škobisová

Urbánková

et al. 2003

Journal of Biological Chemistry

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Section: Fig 1 (A and B) Illustrates The Inhibition Of The Lauric Acmentioning

confidence: 99%

Activating ω-6 Polyunsaturated Fatty Acids and Inhibitory Purine Nucleotides Are High Affinity Ligands for Novel Mitochondrial Uncoupling Proteins UCP2 and UCP3

Žáčková

Škobisová

Urbánková

et al. 2003

Journal of Biological Chemistry

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“…UCP1 is the UCP of brown and beige fat 15 - 18 , but the identity of UCP(s) responsible for I H in all other tissues has remained elusive. It was suggested that all ~50 members of the SLC25 superfamily of mitochondrial solute carriers can contribute to I H 19 , most notably the close UCP1 homologs UCP2 and UCP3 20 - 22 , AAC 7 - 9 , aspartate-glutamate carrier 8 , 23 , dicarboxylate carrier 8 , 24 , and phosphate carrier 25 , 26 . I H may also occur through the lipid phase without protein involvement 27 .…”

Section: Introductionmentioning

confidence: 99%

H+ transport is an integral function of the mitochondrial ADP/ATP carrier

Bertholet

Chouchani

Kazak

et al. 2019

Nature

208

212

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SUMMARY The mitochondrial ADP/ATP carrier (AAC) is a major transport protein of the inner mitochondrial membrane. It exchanges mitochondrial ATP for cytosolic ADP and controls cellular ATP production. In addition, AAC may mediate mitochondrial uncoupling, but this AAC function and its mechanisms remain elusive. Here we record AAC currents directly from inner mitochondrial membrane of various tissues and identify two distinct transport modes: ADP/ATP exchange and H + transport. The AAC-mediated H + current requires free fatty acids and resembles the H + leak via the thermogenic uncoupling protein 1 of brown fat. The ADP/ATP exchange via AAC negatively regulates the H + leak, but without complete inhibition. This suggests that the H + leak and mitochondrial uncoupling could be dynamically controlled by cellular ATP demand and the rate of ADP/ATP exchange. By mediating two distinct transport modes, ADP/ATP exchange and H + leak, AAC intimately connects coupled (ATP production) and uncoupled (thermogenesis) energy conversion in mitochondria.

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“…It is not known to be sensitive to other nucleotides. Other mitochondrial carriers, such as the glutamate [16] and phosphate carriers [17], will catalyse proton conductance in the presence of fatty acids. Specific UCPs (uncoupling proteins) also catalyse inducible proton conductance [18–21].…”

Section: Introductionmentioning

confidence: 99%

Energization-dependent endogenous activation of proton conductance in skeletal muscle mitochondria

Parker

Affourtit

Vidal-Puig

et al. 2008

Biochemical Journal

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Leak of protons into the mitochondrial matrix during substrate oxidation partially uncouples electron transport from phosphorylation of ADP, but the functions and source of basal and inducible proton leak in vivo remain controversial. In the present study we describe an endogenous activation of proton conductance in mitochondria isolated from rat and mouse skeletal muscle following addition of respiratory substrate. This endogenous activation increased with time, required a high membrane potential and was diminished by high concentrations of serum albumin. Inhibition of this endogenous activation by GDP [classically considered specific for UCPs (uncoupling proteins)], carboxyatractylate and bongkrekate (considered specific for the adenine nucleotide translocase) was examined in skeletal muscle mitochondria from wild-type and Ucp3-knockout mice. Proton conductance through endogenously activated UCP3 was calculated as the difference in leak between mitochondria from wild-type and Ucp3-knockout mice, and was found to be inhibited by carboxyatractylate and bongkrekate, but not GDP. Proton conductance in mitochondria from Ucp3-knockout mice was strongly inhibited by carboxyatractylate, bongkrekate and partially by GDP. We conclude the following: (i) at high protonmotive force, an endogenously generated activator stimulates proton conductance catalysed partly by UCP3 and partly by the adenine nucleotide translocase; (ii) GDP is not a specific inhibitor of UCP3, but also inhibits proton translocation by the adenine nucleotide translocase; and (iii) the inhibition of UCP3 by carboxyatractylate and bongkrekate is likely to be indirect, acting through the adenine nucleotide translocase.

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Natural and Azido Fatty Acids Inhibit Phosphate Transport and Activate Fatty Acid Anion Uniport Mediated by the Mitochondrial Phosphate Carrier

Cited by 18 publications

References 44 publications

Activating ω-6 Polyunsaturated Fatty Acids and Inhibitory Purine Nucleotides Are High Affinity Ligands for Novel Mitochondrial Uncoupling Proteins UCP2 and UCP3

Activating ω-6 Polyunsaturated Fatty Acids and Inhibitory Purine Nucleotides Are High Affinity Ligands for Novel Mitochondrial Uncoupling Proteins UCP2 and UCP3

H+ transport is an integral function of the mitochondrial ADP/ATP carrier

Energization-dependent endogenous activation of proton conductance in skeletal muscle mitochondria

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