SIRT3 deficiency decreases oxidative metabolism capacity but increases lifespan in male mice under caloric restriction.

Mitochondrial NAD -dependent protein deacetylase Sirtuin3 (SIRT3) has been proposed to mediate calorie restriction (CR)-dependent metabolic regulation and lifespan extension. Here, we investigated the role of SIRT3 in CR-mediated longevity, mitochondrial function, and aerobic fitness. We report that SIRT3 is required for whole-body aerobic capacity but is dispensable for CR-dependent lifespan extension.

Metabolomic Analysis of Carbohydrate and Amino Acid Changes Induced by Hypoxia in Naked Mole-Rat Brain and Liver.

Hypoxia poses a major physiological challenge for mammals and has significant impacts on cellular and systemic metabolism. As with many other small rodents, naked mole-rats (NMRs; ), who are among the most hypoxia-tolerant mammals, respond to hypoxia by supressing energy demand (i.e.

Obesity-dependent CDK1 signaling stimulates mitochondrial respiration at complex I in pancreatic β-cells.

β-Cell mitochondria play a central role in coupling glucose metabolism with insulin secretion. Here, we identified a metabolic function of cyclin-dependent kinase 1 (CDK1)/cyclin B1-the activation of mitochondrial respiratory complex I-that is active in quiescent adult β-cells and hyperactive in β-cells from obese (/) mice. In WT islets, respirometry revealed that 65% of complex I flux and 49% of state 3 respiration is sensitive to CDK1 inhibition.

Hypoxia induces selective modifications to the acetylome in the brain of zebrafish (Danio rerio).

Reversible protein acetylation is an important regulatory mechanism for modulating protein function. The cellular protein acetylome is in large part dictated by the cellular redox balance, and in particular [NAD]. While the relationship between hypoxia, redox balance, energy charge and resulting mitochondrial dysfunction has been examined in the context of hypoxia-linked pathologies, little is known about the direct effects of decreases in environmental oxygen on reversible lysine acetylation, and the resulting modifications to mitochondrial metabolism.

Ethanol metabolism varies with hypoxia tolerance in ten cyprinid species.

During periods of severe hypoxia or anoxia, Carassius spp. are known for their ability to produce ethanol as their anaerobic end product, which diffuses into the environment thereby reducing the osmotic and acidotic load associated with "anaerobic" glycolysis. However, the relationship between alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activities, key ethanol metabolizing enzymes, and hypoxia tolerance among Carassius spp.

Metabolic programming of the epigenome: host and gut microbial metabolite interactions with host chromatin.

The mammalian gut microbiota has been linked to host developmental, immunologic, and metabolic outcomes. This collection of trillions of microbes inhabits the gut and produces a myriad of metabolites, which are measurable in host circulation and contribute to the pathogenesis of human diseases. The link between endogenous metabolite availability and chromatin regulation is a well-established and active area of investigation; however, whether microbial metabolites can elicit similar effects is less understood.

Using comparative biology to understand how aging affects mitochondrial metabolism.

Lifespan varies considerably among even closely related species, as exemplified by rodents and primates. Despite these disparities in lifespan, most studies have focused on intra-specific aging pathologies, primarily within a select few systems. While mice have provided much insight into aging biology, it is unclear if such a short-lived species lack defences against senescence that may have evolved in related longevous species.

Steep, coincident, and concordant clines in mitochondrial and nuclear-encoded genes in a hybrid zone between subspecies of Atlantic killifish, Fundulus heteroclitus.

Steep genetic clines resulting from recent secondary contact between previously isolated taxa can either gradually erode over time or be stabilized by factors such as ecological selection or selection against hybrids. We used patterns of variation in 30 nuclear and two mitochondrial SNPs to examine the factors that could be involved in stabilizing clines across a hybrid zone between two subspecies of the Atlantic killifish, Fundulus heteroclitus. Increased heterozygote deficit and cytonuclear disequilibrium in populations near the center of the mtDNA cline suggest that some form of reproductive isolation such as assortative mating or selection against hybrids may be acting in this hybrid zone.

Pancreatic β-Cells From Mice Offset Age-Associated Mitochondrial Deficiency With Reduced KATP Channel Activity.

Aging is accompanied by impaired glucose homeostasis and an increased risk of type 2 diabetes, culminating in the failure of insulin secretion from pancreatic β-cells. To investigate the effects of age on β-cell metabolism, we established a novel assay to directly image islet metabolism with NAD(P)H fluorescence lifetime imaging (FLIM). We determined that impaired mitochondrial activity underlies an age-dependent loss of insulin secretion in human islets.

Evidence for a bimodal distribution of hybrid indices in a hybrid zone with high admixture.

The genetic structure of a hybrid zone can provide insights into the relative roles of the various factors that maintain the zone. Here, we use a multilocus approach to characterize a hybrid zone between two subspecies of killifish (Fundulus heteroclitus, Walbaum 1792) found along the Atlantic coast of North America. We first analysed clinal variation along the Atlantic coast using a single-nucleotide polymorphism in the mitochondrial DNA (mtDNA) displacement loop (D-loop) and a panel of nine nuclear microsatellite markers.

Interspecific differences in hypoxia-induced gill remodeling in carp.

The gills of many fish, but in particular those of crucian carp (Carassius carassius) and goldfish (Carassius auratus), are capable of extensive remodeling in response to changes in oxygen (O2), temperature, and exercise. In this study, we investigated the interspecific variation in hypoxia-induced gill modeling and hypoxia tolerance in 10 closely related groups of cyprinids (nine species, with two strains of Cyprinus carpio). There was significant variation in hypoxia tolerance, measured as the O2 tension (P(O2)) at which fish lost equilibrium (LOEcrit), among the 10 groups of carp.

Variation in temperature tolerance among families of Atlantic salmon (Salmo salar) is associated with hypoxia tolerance, ventricle size and myoglobin level.

In fishes, performance failure at high temperature is thought to be due to a limitation on oxygen delivery (the theory of oxygen and capacity limited thermal tolerance, OCLTT), which suggests that thermal tolerance and hypoxia tolerance might be functionally associated. Here we examined variation in temperature and hypoxia tolerance among 41 families of Atlantic salmon (Salmo salar), which allowed us to evaluate the association between these two traits. Both temperature and hypoxia tolerance varied significantly among families and there was a significant positive correlation between critical maximum temperature (CTmax) and hypoxia tolerance, supporting the OCLTT concept.

Intraspecific variation in the thermal plasticity of mitochondria in killifish.

Populations of the Atlantic killifish (Fundulus heteroclitus) inhabit salt marshes and estuaries along the eastern coast of North America from Newfoundland to northern Florida, and are thus exposed to a large range of temperatures. Previous studies have shown higher whole-organism metabolic rates in the northern subspecies (F. h.

The effect of acclimation to hypoxia and sustained exercise on subsequent hypoxia tolerance and swimming performance in goldfish (Carassius auratus).

The objective of this study was to determine whether acclimation to hypoxia and sustained exercise would increase hypoxia tolerance (as indicated by a decrease in critical oxygen tension, P(crit)) and swimming performance in goldfish (Carassius auratus), and to investigate the relationship between changes in performance and gill remodelling and tissue metabolic capacity. Goldfish were acclimated to either hypoxia (48 h at 0.3 mg O(2) l(-1)) or sustained exercise (48 h at 70% of critical swimming speed, U(crit)) and then P(crit) and U(crit) were determined in normoxia (10 mg O(2) l(-1)) and hypoxia (1 mg O(2) l(-1)) and compared with values from control fish.