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Proton gradient drives atp synthesis11/24/2023 ![]() Glucose, fatty acids, and amino acids (glutamine shown here) undergo catabolism to feed into the tricarboxylic acid cycle (TCA cycle), which generates substrates for the electron transport chain (ETC). (A) Substrate supply for mitochondrial respiration. Regardless of the exact mechanism, the transfer of two electrons from NADH results in the pumping of four protons. Though the mechanism linking electron transfer to proton pumping remains unclear, one hypothesis speculates an indirect pumping of two protons via a conformation-coupled manner and the direct pumping of the other two protons via the ubiquinone redox reaction, while another hypothesis suggests that changes in the conformation and density of water in Complex I dictates the proton translocation. This electron transfer induces the pumping of protons by Complex I from the matrix into the intermembrane space. The electrons from NADH are passed to ubiquinone (CoQ) through a chain of co-factors including a flavin mononucleotide (FMN) followed by seven low to high potential iron-sulfur (FeS) clusters in Complex I to enter the Q cycle, where CoQ is reduced to ubiquinol (QH 2). NADH and FADH 2 generated by the TCA cycle donate electrons to the ETC at either Complex I (NADH:ubiquinone oxidoreductase) or Complex II (succinate dehydrogenase), respectively ( Fig. The ETC is embedded within the extensive inner membrane of the mitochondrion, in close proximity to the mitochondrial matrix in which the TCA cycle is localized ( Fig. Here we summarize the reactions that occur in the ETC to produce energy, but for a more detailed review, refer to Zhao et al. However, the molecules derived from these processes are used in the tricarboxylic acid (TCA) cycle to generate substrates that enter the ETC for oxidative phosphorylation. The processes for the catabolism of glucose (via glycolysis and subsequent pyruvate oxidation), fatty acids (via fatty acid β-oxidation), and amino acids (via oxidative deamination and transamination) are reviewed in detail elsewhere. ![]() ![]() Further, we will compare current methodologies to measure bioenergetic function and mitochondrial ROS production.Ĭellular metabolism comprises the utilization of carbohydrates, fats, and proteins, to synthesize energy. In this review, we will provide an overview of the function of the ETC, focusing on oxidative phosphorylation and its relationship to ROS production. ĭespite this variation between cell types, mitochondrial ATP generation and ROS production are intimately linked through function of the electron transport chain (ETC), and thus efficient measurement of ETC function can provide insight into mechanisms of physiology and disease pathogenesis. In contrast, endothelial cells rely more heavily on glycolysis than mitochondria for ATP, but mitochondrial ROS production is essential for endothelial homeostatic signaling. For example, cardiomyocytes rely on mitochondria to supply >95% of the energy required for their function. Notably, the importance of each of these functions varies by cell type. Since then, it has become apparent that mitochondria are highly dynamic organelles that contribute to cellular homeostasis not only through maintaining adenosine triphosphate (ATP) levels, but also through the generation of low levels of ROS for cell signaling, and that dysfunction in either of these processes can propagate pathology. Less than a decade later came the first reports that the organelle generated reactive oxygen species (ROS) as a byproduct of cellular respiration. In 1957, Peter Siekevitz branded the mitochondrion the “powerhouse” of the cell.
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