Supercomplex organization of the electron transfer system in marine bivalves, a model of extreme longevity

The mitochondrial oxidative stress theory of aging (MOSTA) suggests that the organelle’s decay contributes to the aging phenotype via exacerbated oxidative stress, loss of organ coordination and energetics, cellular integrity and activity of the mitochondrial electron transfer system (ETS). Recent advances in understanding the structure of the ETS show that the enzymatic complexes responsible for oxidative phosphorylation are arranged in supramolecular structures called supercomplexes that lose organization during aging. Their exact role and universality among organisms are still under debate. Here, we take advantage of marine bivalves as an aging model to compare the structure of the ETS among species ranging from 28 to 507 years in maximal lifespan. Our results show that regardless of lifespan, the bivalve ETS is arrayed as a set of supercomplexes. However, bivalve species display varying degrees ETS supramolecular organization with the highest supercomplex structures found in A. islandica, the longest-lived of the bivalve species under study. We discuss this comparative model in light of differences in the nature and stoichiometry of these complexes, and highlight the potential link between the complexity of these superstructures and longer lifespans.

Skeletal Muscle Adaptations to Exercise Training in Young and Aged Horses

In aged humans, low-intensity exercise increases mitochondrial density, function and oxidative capacity, decreases the prevalence of hybrid fibers, and increases lean muscle mass, but these adaptations have not been studied in aged horses. Effects of age and exercise training on muscle fiber type and size, satellite cell abundance, and mitochondrial volume density (citrate synthase activity; CS), function (cytochrome c oxidase activity; CCO), and integrative (per mg tissue) and intrinsic (per unit CS) oxidative capacities were evaluated in skeletal muscle from aged (n = 9; 22 ± 5 yr) and yearling (n = 8; 9.7 ± 0.7 mo) horses. Muscle was collected from the gluteus medius (GM) and triceps brachii at wk 0, 8, and 12 of exercise training. Data were analyzed using linear models with age, training, muscle, and all interactions as fixed effects. At wk 0, aged horses exhibited a lower percentage of type IIx (p = 0.0006) and greater percentage of hybrid IIa/x fibers (p = 0.002) in the GM, less satellite cells per type II fiber (p = 0.03), lesser integrative and intrinsic (p≤ 0.04) CCO activities, lesser integrative oxidative phosphorylation capacity with complex I (PCI; p = 0.02) and maximal electron transfer system capacity (ECI+II; p = 0.06), and greater intrinsic PCI, ECI+II, and electron transfer system capacity with complex II (ECII; p≤ 0.05) than young horses. The percentage of type IIx fibers increased (p < 0.0001) and of type IIa/x fibers decreased (p = 0.001) in the GM, and the number of satellite cells per type II fiber increased (p = 0.0006) in aged horses following exercise training. Conversely, the percentage of type IIa/x fibers increased (p ≤ 0.01) and of type IIx fibers decreased (p ≤ 0.002) in young horses. Integrative maximal oxidative capacity (p ≤ 0.02), ECI+II (p ≤ 0.07), and ECII (p = 0.0003) increased for both age groups from wk 0 to 12. Following exercise training, aged horses had a greater percentage of IIx (p ≤ 0.002) and lesser percentage of IIa/x fibers (p ≤ 0.07), and more satellite cells per type II fiber (p = 0.08) than young horses, but sustained lesser integrative and intrinsic CCO activities (p≤ 0.04) and greater intrinsic PCI, ECI+II, and ECII (p≤ 0.05). Exercise improved mitochondrial measures in young and aged horses; however, aged horses showed impaired mitochondrial function and differences in adaptation to exercise training.

Divergences in the control of mitochondrial respiration are associated with lifespan variation in marine bivalves

The role played by mitochondrial function in the aging process has been a subject of intense debate in the past few decades, as part of the efforts to understand the mechanistic basis of longevity. The mitochondrial oxidative stress theory of aging (MOSTA) suggests that a progressive decay of this organelle’s function leads to an exacerbation of oxidative stress, with deleterious impact on mitochondrial structure and DNA, ultimately promoting aging. Among the traits suspected to be associated with longevity is the variation in regulation of oxidative phosphorylation, potentially impacting the management of oxidative stress. Longitudinal studies using the framework of metabolic control analysis have shown age-related differences in flux control of respiration, but this approach has seldom been taken on a comparative scale. Using four species of marine bivalves exhibiting a large range of maximum lifespans (from 28y to 507y), we report lifespan-related differences in flux control at different steps of the electron transfer system. Increased longevity was characterized by a lower control by NADH- (complex I-linked) and Succinate- (complex II- linked) pathways, while respiration was strongly controlled by complex IV when compared to shorter-lived species. Complex III exterted a strong control over respiration in all species. Furthermore, high longevity was associated with higher citrate synthase activity, and lower ATP synthase activity. Relieving the control exerted by the electron entry pathways could be advantageous for reaching a higher longevity, leading to an increased control by complex IV, the final electron acceptor in the electron transfer system.

Reorganization energies and spectral densities for electron transfer problems in charge transport materials

Various contributions to the outer reorganization energy of an electron transfer system and their theoretical and computational aspects have been discussed.

Extracellular electron transfer powers flavinylated extracellular reductases in Gram-positive bacteria

Mineral-respiring bacteria use a process called extracellular electron transfer to route their respiratory electron transport chain to insoluble electron acceptors on the exterior of the cell. We recently characterized a flavin-based extracellular electron transfer system that is present in the foodborne pathogenListeria monocytogenes, as well as many other Gram-positive bacteria, and which highlights a more generalized role for extracellular electron transfer in microbial metabolism. Here we identify a family of putative extracellular reductases that possess a conserved posttranslational flavinylation modification. Phylogenetic analyses suggest that divergent flavinylated extracellular reductase subfamilies possess distinct and often unidentified substrate specificities. We show that flavinylation of a member of the fumarate reductase subfamily allows this enzyme to receive electrons from the extracellular electron transfer system and supportL. monocytogenesgrowth. We demonstrate that this represents a generalizable mechanism by finding that aL. monocytogenesstrain engineered to express a flavinylated extracellular urocanate reductase uses urocanate by a related mechanism and to a similar effect. These studies thus identify an enzyme family that exploits a modular flavin-based electron transfer strategy to reduce distinct extracellular substrates and support a multifunctional view of the role of extracellular electron transfer activities in microbial physiology.

Inverse correlation between heme synthesis and the Warburg effect in cancer cells

AbstractsCancer cells show a bias toward the glycolytic system over the conventional mitochondrial electron transfer system for obtaining energy. This biased metabolic adaptation is called the Warburg effect. Cancer cells also exhibit a characteristic metabolism, a decreased heme synthesizing ability. Here we show that heme synthesis and the Warburg effect are inversely correlated. We used human gastric cancer cell lines to investigate glycolytic metabolism and electron transfer system toward promotion/inhibition of heme synthesis. Under hypoxic conditions, heme synthesis was suppressed and the glycolytic system was enhanced. Addition of a heme precursor for the promotion of heme synthesis led to an enhanced electron transfer system and inhibited the glycolytic system and vice versa. Enhanced heme synthesis leads to suppression of cancer cell proliferation by increasing intracellular reactive oxygen species levels. Collectively, the promotion of heme synthesis in cancer cells eliminated the Warburg effect by shifting energy metabolism from glycolysis to oxidative phosphorylation.