Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of trifluoperazine on the respiration of porcine liver and skeletal muscle mitochondria was investigated by polarographic and spectroscopic techniques. Low concentrations of trifluoperazine (88 nmol/mg protein) inhibited both the ADP- and Ca2+-stimulated oxidation of succinate, and reduced the values of the respiratory control index and the ADP/O and Ca2+/O ratio. High concentrations inhibited both succinate and ascorbate plus tetramethyl-p-phenylenediame (TMPD) oxidations, and uncoupler (carbonyl cyanide p-trifluromethoxyphenylhydrazone) and Ca2+-stimulated respiration. Porcine liver mitochondria were more sensitive to trifluoperazine than skeletal muscle mitochondria. Trifluoperazine inhibited the electron transport of succinate oxidation of skeletal muscle mitochondria within the cytochrome b-c1 and cytochrome c1-aa3 segments of the respiratory chain system. 233 nmol trifluoperazine/mg protein inhibited the aerobic steady-state reduction of cytochrome c1 by 92% with succinate as substrate, and of cytochrome c and cytochrome aa3 by 50-60% with ascorbate plus TMPD as electron donors. Trifluoperazine can thus inhibit calmodulin-independent reactions particularly when used at high concentrations.
 ...
PMID:Effect of trifluoperazine on skeletal muscle mitochondrial respiration. 683 Jul 68

Mitochondria that contain Ca2+ can be induced by a variety of triggering agents and conditions to undergo a permeability transition (PT); the inner membrane becomes nonselectively permeable to small solutes. Mastoparan, an amphipathic peptide from wasp venom, has recently been reported to induce this transition (Pfeiffer et al., 1995, J. Biol. Chem. 270,4923). We have examined the effect on the permeability of isolated rat liver mitochondria of a second amphipathic peptide, the signal sequence of cytochrome oxidase subunit IV from Neurospora crassa (pCoxIV, amino acids 3-22), which targets subunit IV to its mitochondrial location. Permeability increases were visualized via mitochondrial swelling with the following results. (1) pCoxIV (5-100 microM) induced concentration-dependent mitochondrial swelling. Control peptides from the N- and C-termini of the voltage-dependent anion-selective channel had no such effect. (2) Swelling required mitochondrial energization; it was eliminated or halted by the uncoupler carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone. (3) Peptide-induced swelling was slowed by increasing concentrations of KCl. (4) Swelling was enhanced by inorganic phosphate (<1 mM). (5) Trifluoperazine (50 microM), propranolol (0.5 mM), and dibucaine (0.5 mM) were potent inhibitors of peptide-induced swelling, whereas other inhibitors of the classical PT (cyclosporin A, EGTA, and ADP) inhibited only partially. (6) pCoxIV opened a pore rather than disrupting mitochondrial membrane structure, but 50% inhibition of peptide-induced swelling required polyethylene glycol of molecular weight substantially larger than that needed to inhibit the Ca2+-induced PT to the same extent. In summary, pCoxIV opens a pore in isolated mitochondria. The dependence of pore opening on membrane potential and the inhibition of the peptide-induced permeability increase by increasing salt concentration suggest that this effect of the signal peptide is related to its interactions with mitochondria during protein import. The peptide-induced pore appears, however, to be distinct from both the classical permeability transition pore and the mastoparan-induced permeability increase.
 ...
PMID:A mitochondrial signal peptide from Neurospora crassa increases the permeability of isolated rat liver mitochondria. 895 Oct 36