Mitochondrial Function and Bioenergetics
摘要
Up to the present time, electron transport enzymes and ATP synthase in the mitochondrial supercomplexMitochondrial supercomplex, ribosomal machinery, genome function, and overall cellular function have become increasingly complex as cells became diversified and specialized into organs. Not all our genes are known to be necessary for life, but many of the other genes likely provide redundancy or duplicity for ensuring fitness for survival, synergy, repair, replacement, and adaptations for stress or injury, among other actions. The number of nuclear genes regulating mitochondrial function is now very high. The basic chemiosmotic mechanism is probably highly conserved but many added mitochondrial enzymes now facilitate the processes of glycolysis, carbon turnover in the tricarboxylic acid cycle, the electron transport system, and ATP synthesis. The details of these reactions in modern cardiac mitochondria are described here and utilize equations to understand the transfer of protons and electrons with metabolism from substrates and O2 to water and carbon dioxide. Photosynthetic bacteria, algae, and plants utilize light for chemiosmosisChemiosmosis to make ATP and sugars as substrates for all non-photosynthesizing animals. In glycolysis (fermentation) sugars are broken down to reduce a universally established cofactor, the nicotinamide-adenine-dinucleotide complex, and to make substrate-level ATP; further metabolism by chemiosmosisChemiosmosis and oxidative phosphorylation produces much more ATP. Other universal and important cofactors that transfer electrons and protons in a continuous cycle are nicotinamide-adenine-dinucleotide-phosphate and the flavoenzymes. Mobile electron carriers (ubiquinones) within the respiratory complexes I, III, and IV promote proton pumping and sequentially begin with a low affinity for electrons with the highest affinity for electrons during the final reduction of O2 to water. Proton pumping provides for high mitochondrial redox, pH, and membrane charge potentials. ATP consumption has a tendency to lower these potentials during re-phosphorylation at complex V because of proton reentry, which then stimulates respiration (oxidation) to restore the potentials to basal levels. Because of the variability of ATP demand, as in exercise vs. rest, cardiac mitochondria are well adapted to rapidly reset the level of bioenergetic activity. Bioenergetics can be studied in isolated hearts and in isolated mitochondria using ion-selective fluorescence dyes, ADP, substrates, activators, and inhibitors.