Part I Molecular System Bioenergetics: Basic Principles, Organization, and Dynamics of Cellular Energetics

Energy metabolism in living organisms is supported by the oxidation of carbohydrates and lipids, which are metabolized with several similarities as well as major differences. Conversely to prokaryotes and inferior eukaryotes, a complete oxidation leading to CO2 and H2O formation is mandatory. Our knowledge about oxidative phosphorylation is mostly based on simplified in vitro models, i.e., isolated mitochondria where only those parameters included in the experimental systems can be appreciated. However, relationships between mitochondria and the host cell are of major importance in the regulation of the pathway of ATP synthesis and oxygen consumption by the respiratory chain. By determining the respective rate of glucose or fatty acid oxidation, cellular intermediary metabolism affects the ratio between NADH and FADH2, upstream of the Krebs cycle, thus affecting the yield ATP synthesis. The mechanism for translocating reducing equivalents across the mitochondrial inner membrane (the malate–aspartate and glycerol-3phosphate–dihydroxyacetone phosphate shuttles) also plays an important role. Indeed, because of such characteristics of electron supply to the respiratory chain, oxidative phosphorylation activity also participates in the determination of the ratio of NADH to FADH2 oxidation, by modulation of the protonmotive force. Besides the role of thermodynamic and kinetic constraints applied to the oxidative phosphorylation pathway, it now appears that the supramolecular organization of oxidative phosphorylation and of cellular energy circuits introduces new regulatory factors of oxidative phosphorylation.