Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the energy requirement of mitochondrial protein import with a simplified system containing only isolated yeast mitochondria, energy sources and a purified precursor protein. This precursor was a fusion protein composed of 22 residues of the cytochrome oxidase subunit IV pre-sequence fused to mouse dihydrofolate reductase. Import of this protein required not only an energized inner membrane, but also ATP. ATP could be replaced by GTP, but not by CTP, TTP or non-hydrolyzable ATP analogs. Added ATP did not increase the membrane potential of respiring mitochondria; it supported import even if the proton-translocating mitochondrial ATPase and the entry of ATP into the matrix were blocked. We conclude that ATP exerts its effect on mitochondrial protein import outside the inner membrane.
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PMID:Both ATP and an energized inner membrane are required to import a purified precursor protein into mitochondria. 303 90

During oxidative phosphorylation most of the protons pumped out to the cytosol across the mitochondrial inner membrane return to the matrix through the ATP synthase, driving ATP synthesis. However, some of them leak back to the matrix through a proton-conductance pathway in the membrane. When the ATP synthase is inhibited with oligomycin and ATP is not being synthesized, all of the respiration is used to drive the proton leak. We report here that Mg(2+) inhibits the proton conductance in rat skeletal-muscle mitochondria. Addition of Mg(2+) inhibited both oligomycin-inhibited respiration and the proton conductance, while removal of Mg(2+) using EDTA activated these processes. The proton conductance was inhibited by more than 80% as free Mg(2+) was raised from 25 nM to 220 microM. Half-maximal inhibition occurred at about 1 microM free Mg(2+), which is close to the contaminating free Mg(2+) concentration in our incubations in the absence of added magnesium chelators. ATP, GTP, CTP, TTP or UTP at a concentration of 1 mM increased the oligomycin-inhibited respiration rate by about 50%. However, these NTP effects were abolished by addition of 2 mM Mg(2+) and any NTP-stimulated proton conductance was explained completely by chelation of endogenous free Mg(2+). The corresponding nucleoside diphosphates (ADP, GDP, CDP, TDP or UDP) at 1 mM had no effect on oligomycin-inhibited respiration. We conclude that proton conductance in rat skeletal-muscle mitochondria is very sensitive to free Mg(2+) concentration but is insensitive to NTPs or NDPs at 1 mM.
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PMID:Effects of magnesium and nucleotides on the proton conductance of rat skeletal-muscle mitochondria. 1079 33