RESUMO
Mitochondria metabolize almost all the oxygen that we consume, reducing it to water by cytochrome c oxidase (CcO). CcO maximizes energy capture into the protonmotive force by pumping protons across the mitochondrial inner membrane. Forty years after the H+/e- stoichiometry was established, a consensus has yet to be reached on the route taken by pumped protons to traverse CcO's hydrophobic core and on whether bacterial and mitochondrial CcOs operate via the same coupling mechanism. To resolve this, we exploited the unique amenability to mitochondrial DNA mutagenesis of the yeast Saccharomyces cerevisiae to introduce single point mutations in the hydrophilic pathways of CcO to test function. From adenosine diphosphate to oxygen ratio measurements on preparations of intact mitochondria, we definitely established that the D-channel, and not the H-channel, is the proton pump of the yeast mitochondrial enzyme, supporting an identical coupling mechanism in all forms of the enzyme.
Assuntos
Complexo IV da Cadeia de Transporte de Elétrons/química , Heme/química , Oxirredutases/química , Bactérias/metabolismo , Cobre/química , Cobre/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Transporte de Íons , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , Oxirredução , Oxirredutases/metabolismo , Oxigênio/metabolismo , Bombas de Próton/metabolismo , Prótons , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMO
Meroterpenoids discovered in Rhododendrons species possess unique chemical structures and biological activities and are expected to become new drug targets for Alzheimer's disease, metabolic disorders, and chronic kidney disease, and these compounds have attracted increasing attention in recent years. In this study, Rhododendron meroterpenoids and their structures, classifications, racemate distribution, biosynthetic pathways, chemical synthesis, and bioactivities are reviewed prior to 2023.
Assuntos
Rhododendron , Terpenos , Rhododendron/química , Terpenos/química , Terpenos/farmacologia , Terpenos/isolamento & purificação , Terpenos/síntese química , Humanos , Estrutura Molecular , Descoberta de DrogasRESUMO
DNAzyme motor systems using gold nanoparticles (AuNPs) as scaffolds are useful for biosensing and in situ amplification because these systems are free of protein enzymes, isothermal, homogeneous, and sensitive. However, detecting different targets using the available DNAzyme motor techniques requires redesigns of the DNAzyme motor. We report here a toehold-exchange translator and the translator-mediated DNAzyme motor systems, which enable sensitive responses to various nucleic acid targets using the same DNAzyme motor without requiring redesign. The translator is able to efficiently convert different nucleic acid targets into a specific output DNA that further activates the pre-silenced DNAzyme motor and consequently initiates the autonomous walking of the DNAzyme motor. Simply adjusting the target-binding region of the translator enables the same DNAzyme motor system to respond to various nucleic acid targets. The translator-mediated DNAzyme motor system is able to detect as low as 2.5 pM microRNA-10b and microRNA-21 under room temperature without the need of separation or washing. We further demonstrate the versatility of the translator and the DNAzyme motor by successful construction and operation of four logic gates, including OR, AND, NOR, and NAND logic gates. These logic gates use two microRNA targets as inputs and generate amplified fluorescence signals from the operation of the same DNAzyme motor. Incorporation of the toehold-exchange translator into the DNAzyme motor technology improves the biosensing applications of DNA motors to diverse nucleic acid targets.