Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.6.3.14 (ATP synthase)
7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oligomycin A, an inhibitor of mitochondrial ATP synthase, provokes simultaneous and different responses in IPLB-LdFB insect cell line. The oligomycin A treatment causes mitochondrial loss, increase in reactive oxygen species (ROS), destabilization/reorganization of the actin microfilaments and, finally, autophagic cell death. We speculate that oligomycin A affects the mitochondria and that the impairment of these organelles leads to the generation of ROS in quantities that exceed the antioxidant capacity of the cell. This in turn would lead to a feedback loop of increased mitochondrial impairment, amplification of ROS production and the removal of damaged organelles through autophagy.
...
PMID:Oligomycin A and the IPLB-LdFB insect cell line: actin and mitochondrial responses. 1809 49

Incubation of boar spermatozoa in a capacitation medium with oligomycin A, a specific inhibitor of the F0 component of the mitochondrial ATP synthase, induced an immediate and almost complete immobilisation of cells. Oligomycin A also inhibited the ability of spermatozoa to achieve feasible in vitro capacitation (IVC), as measured through IVC-compatible changes in motility patterns, tyrosine phosphorylation levels of the acrosomal p32 protein, membrane fluidity and the ability of spermatozoa to achieve subsequent, progesterone-induced in vitro acrosome exocytosis (IVAE). Both inhibitory effects were caused without changes in the rhythm of O2 consumption, intracellular ATP levels or mitochondrial membrane potential (MMP). IVAE was accompanied by a fast and intense peak in O2 consumption and ATP levels in control spermatozoa. Oligomycin A also inhibited progesterone-induced IVAE as well as the concomitant peaks of O2 consumption and ATP levels. The effect of oligomycin on IVAE was also accompanied by concomitant alterations in the IVAE-induced changes on intracellular Ca(2+) levels and MMP. Our results suggest that the oligomycin A-sensitive mitochondrial ATP-synthase activity is instrumental in the achievement of an adequate boar sperm motion pattern, IVC and IVAE. However, this effect seems not to be linked to changes in the overall maintenance of adequate energy levels in stages other than IVAE.
...
PMID:Oligomycin A-induced inhibition of mitochondrial ATP-synthase activity suppresses boar sperm motility and in vitro capacitation achievement without modifying overall sperm energy levels. 2531 79

Cytoplasmic alkalinization and extracellular adenosine triphosphate (ATP) signals are required for migration of chemokineactivated neutrophils, but the precise functions remain unclear. In this work, the effect of the plasma membrane-expressed F0F1-ATP synthase (FATPase) on human neutrophils was examined. We found F-ATPase to be involved in cytoplasm proton extrusion and extracellular ATP generation. Oligomycin A, an F-ATPase inhibitor that blocks proton transfer, inhibited cytoplasmic alkalinization, extracellular ATP generation, adhesion and chemotaxis in N-formyl-Met-Leu-Phe (fMLP)-stimulated neutrophils; however, adenosine diphosphate (ADP), a substrate and activator of F-ATPase, had the opposite effect. Further analysis revealed that cell surface F-ATPase can translocate to the leading edge of directional fMLP-stimulated neutrophils toward ADP hydrolyzed from pannexin 1 channel-released ATP, followed by F-ATPase-catalyzed ATP regeneration using ADP and protons transferred from the cytoplasm. Therefore, the membrane-expressed F-ATPase regulates human neutrophil migration via cytoplasm proton extrusion and extracellular ATP generation.
...
PMID:The F0F1 ATP synthase regulates human neutrophil migration through cytoplasmic proton extrusion coupled with ATP generation. 2884 71

Dendritic spine injury underlies synaptic failure in many neurological disorders. Mounting evidence suggests a mitochondrial pathway of local nonapoptotic caspase signaling in mediating spine pruning. However, it remains unclear whether this caspase signaling plays a key role in spine loss when severe mitochondrial functional defects are present. The answer to this question is critical especially for some pathological states, in which mitochondrial deficits are prominent and difficult to fix. F1Fo ATP synthase is a pivotal mitochondrial enzyme and the dysfunction of this enzyme involves in diseases with spinopathy. Here, we inhibited F1Fo ATP synthase function in primary cultured hippocampal neurons by using non-lethal oligomycin A treatment. Oligomycin A induced mitochondrial defects including collapsed mitochondrial membrane potential, dissipated ATP production, and elevated reactive oxygen species (ROS) production. In addition, dendritic mitochondria underwent increased fragmentation and reduced positioning to dendritic spines along with increased caspase 3 cleavage in dendritic shaft and spines in response to oligomycin A. Concurring with these dendritic mitochondrial changes, oligomycin A-insulted neurons displayed spine loss and altered spine architecture. Such oligomycin A-mediated changes in dendritic spines were substantially prevented by the inhibition of caspase activation by using a pan-caspase inhibitor, quinolyl-valyl-O-methylaspartyl-[-2,6-difluorophenoxy]-methyl ketone (Q-VD-OPh). Of note, the administration of Q-VD-OPh showed no protective effect on oligomycin A-induced mitochondrial dysfunction. Our findings suggest a pivotal role of caspase 3 signaling in mediating spine injury and the modulation of caspase 3 activation may benefit neurons from spine loss in diseases, at least, in those with F1Fo ATP synthase defects.
...
PMID:Caspase inhibition rescues F1Fo ATP synthase dysfunction-mediated dendritic spine elimination. 3306 41

This work analyzes the effects of red LED light on mammalian sperm mitochondrial function, using the pig as an animal model. Liquid-stored pig semen was stimulated with red-light for 1, 5 and 10 min in the presence or absence of oligomycin A, a specific inhibitor of mitochondrial ATP synthase, or carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP), a specific disruptor of mitochondrial electron chain. Whereas exposure for 1 and 5 min significantly (p < 0.05) decreased total motility and intracellular ATP levels, irradiation for 10 min induced the opposite effect. Oligomycin A abolished the light-effects on intracellular ATP levels, O₂ consumption and mitochondrial membrane potential, whereas compared to non-irradiated samples, FCCP significantly (p < 0.05) increased O₂ consumption when sperm were irradiated for 1 min. Both oligomycin A and FCCP significantly (p < 0.05) decreased total motility. Red-light increased cytochrome c oxidase activity with a maximal effect after 5 min of irradiation, which was abolished by both oligomycin A and FCCP. In conclusion, red-light modulates sperm mitochondrial function via electron chain activity in an exposition, time-dependent manner.
...
PMID:Red LED Light Acts on the Mitochondrial Electron Chain of Mammalian Sperm via Light-Time Exposure-Dependent Mechanisms. 3325 77

---