scholarly journals Prenatal acoustic programming of mitochondrial function for high temperatures in an arid-adapted bird

2021 ◽  
Vol 288 (1964) ◽  
Author(s):  
Eve Udino ◽  
Julia M. George ◽  
Matthew McKenzie ◽  
Anaïs Pessato ◽  
Ondi L. Crino ◽  
...  
Keyword(s):  
High Temperatures ◽  
Prenatal Exposure ◽  
Mitochondrial Function ◽  
Production Efficiency ◽  
Developmental Programming ◽  
Atp Production ◽  
Thermal Environments ◽  
Mitochondrial Efficiency ◽  
Underlying Mechanisms ◽  
Acoustic Sensitivity

Sound is an essential source of information in many taxa and can notably be used by embryos to programme their phenotypes for postnatal environments. While underlying mechanisms are mostly unknown, there is growing evidence for the involvement of mitochondria—main source of cellular energy (i.e. ATP)—in developmental programming processes. Here, we tested whether prenatal sound programmes mitochondrial metabolism. In the arid-adapted zebra finch, prenatal exposure to ‘heat-calls’—produced by parents incubating at high temperatures—adaptively alters nestling growth in the heat. We measured red blood cell mitochondrial function, in nestlings exposed prenatally to heat- or control-calls, and reared in contrasting thermal environments. Exposure to high temperatures always reduced mitochondrial ATP production efficiency. However, as expected to reduce heat production, prenatal exposure to heat-calls improved mitochondrial efficiency under mild heat conditions. In addition, when exposed to an acute heat-challenge, LEAK respiration was higher in heat-call nestlings, and mitochondrial efficiency low across temperatures. Consistent with its role in reducing oxidative damage, LEAK under extreme heat was also higher in fast growing nestlings. Our study therefore provides the first demonstration of mitochondrial acoustic sensitivity, and brings us closer to understanding the underpinning of acoustic developmental programming and avian strategies for heat adaptation.

scholarly journals Dramatic changes in mitochondrial substrate use at critically high temperatures: a comparative study using Drosophila

2021 ◽  
Vol 224 (6) ◽  
pp. jeb240960
Author(s):  
Lisa Bjerregaard Jørgensen ◽  
Johannes Overgaard ◽  
Florence Hunter-Manseau ◽  
Nicolas Pichaud
Keyword(s):  
High Temperatures ◽  
Heat Tolerance ◽  
Mitochondrial Function ◽  
Complex I ◽  
Mitochondrial Oxygen Consumption ◽  
Alternative Substrates ◽  
Atp Production ◽  
C Complex ◽  
Titration Protocol ◽  
Catalytic Capacity

ABSTRACTEctotherm thermal tolerance is critical to species distribution, but at present the physiological underpinnings of heat tolerance remain poorly understood. Mitochondrial function is perturbed at critically high temperatures in some ectotherms, including insects, suggesting that heat tolerance of these animals is linked to failure of oxidative phosphorylation (OXPHOS) and/or ATP production. To test this hypothesis, we measured mitochondrial oxygen consumption rate in six Drosophila species with different heat tolerance using high-resolution respirometry. Using a substrate–uncoupler–inhibitor titration protocol, we examined specific steps of the electron transport system to study how temperatures below, bracketing and above organismal heat limits affect mitochondrial function and substrate oxidation. At benign temperatures (19 and 30°C), complex I-supported respiration (CI-OXPHOS) was the most significant contributor to maximal OXPHOS. At higher temperatures (34, 38, 42 and 46°C), CI-OXPHOS decreased considerably, ultimately to very low levels at 42 and 46°C. The enzymatic catalytic capacity of complex I was intact across all temperatures and accordingly the decreased CI-OXPHOS is unlikely to be caused directly by hyperthermic denaturation/inactivation of complex I. Despite the reduction in CI-OXPHOS, maximal OXPHOS capacity was maintained in all species, through oxidation of alternative substrates – proline, succinate and, particularly, glycerol-3-phosphate – suggesting important mitochondrial flexibility at temperatures exceeding the organismal heat limit. Interestingly, this failure of CI-OXPHOS and compensatory oxidation of alternative substrates occurred at temperatures that correlated with species heat tolerance, such that heat-tolerant species could defend ‘normal’ mitochondrial function at higher temperatures than sensitive species. Future studies should investigate why CI-OXPHOS is perturbed and how this potentially affects ATP production rates.

scholarly journals Exercise rescues mitochondrial coupling in aged skeletal muscle: a comparison of different modalities in preventing sarcopenia

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Colin Harper ◽  
Venkatesh Gopalan ◽  
Jorming Goh
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Function ◽  
Fiber Type ◽  
Skeletal Muscle Function ◽  
Atp Production ◽  
Muscle Aging ◽  
Age Related ◽  
Key Factor ◽  
Underlying Mechanisms ◽  
Skeletal Muscle Aging

AbstractSkeletal muscle aging is associated with a decline in motor function and loss of muscle mass- a condition known as sarcopenia. The underlying mechanisms that drive this pathology are associated with a failure in energy generation in skeletal muscle, either from age-related decline in mitochondrial function, or from disuse. To an extent, lifelong exercise is efficacious in preserving the energetic properties of skeletal muscle and thus may delay the onset of sarcopenia. This review discusses the cellular and molecular changes in skeletal muscle mitochondria during the aging process and how different exercise modalities work to reverse these changes. A key factor that will be described is the efficiency of mitochondrial coupling—ATP production relative to O2 uptake in myocytes and how that efficiency is a main driver for age-associated decline in skeletal muscle function. With that, we postulate the most effective exercise modality and protocol for reversing the molecular hallmarks of skeletal muscle aging and staving off sarcopenia. Two other concepts pertinent to mitochondrial efficiency in exercise-trained skeletal muscle will be integrated in this review, including- mitophagy, the removal of dysfunctional mitochondrial via autophagy, as well as the implications of muscle fiber type changes with sarcopenia on mitochondrial function.

scholarly journals Dramatic changes in mitochondrial substrate use at critically high temperatures: a comparative study using Drosophila

2020 ◽  
Author(s):  
Lisa Bjerregaard Jørgensen ◽  
Johannes Overgaard ◽  
Florence Hunter-Manseau ◽  
Nicolas Pichaud
Keyword(s):  
High Temperatures ◽  
Heat Tolerance ◽  
Mitochondrial Function ◽  
Complex I ◽  
Mitochondrial Oxygen Consumption ◽  
Alternative Substrates ◽  
Atp Production ◽  
Consumption Rates ◽  
C Complex ◽  
Titration Protocol

AbstractEctotherm thermal tolerance is critical to species distribution, but at present the physiological underpinnings of heat tolerance remain poorly understood. Mitochondrial function is perturbed at critically high temperatures in some ectotherms, including insects, suggesting that heat tolerance of these animals is linked to failure of oxidative phosphorylation (OXPHOS) and/or ATP production. To test this hypothesis we measured mitochondrial oxygen consumption rates in six Drosophila species with different heat tolerance using high-resolution respirometry. Using a substrate-uncoupler-inhibitor titration protocol we examined specific steps of the electron transport system to study how temperatures below, bracketing and above organismal heat limits affected mitochondrial function and substrate oxidation. At benign temperatures (19 and 30°C), complex I-supported respiration (CI-OXPHOS) was the most significant contributor to maximal OXPHOS. At higher temperatures (34, 38, 42 and 46°C), CI-OXPHOS decreased considerably, ultimately to very low levels at 42 and 46°C. The enzymatic catalytic capacity of complex I was intact across all temperatures and accordingly the decreased CI-OXPHOS is unlikely to be caused directly by hyperthermic denaturation/inactivation of complex I. Despite the reduction in CI-OXPHOS, maximal OXPHOS capacities were maintained in all species, through oxidation of alternative substrates; proline, succinate and, particularly, glycerol-3-phosphate, suggesting important mitochondrial flexibility at temperatures exceeding the organismal heat limit. Interestingly, this compensatory oxidation of alternative substrates occurred at temperatures that tended to correlate with species heat tolerance, such that heat-tolerant species could defend “normal” mitochondrial function at higher temperatures than sensitive species. Future studies should investigate why CI-OXPHOS is perturbed and how this potentially affects ATP production rates.

scholarly journals Implication of Mitochondrial Cytoprotection in Human Islet Isolation and Transplantation

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Yong Wang ◽  
Joshua E. Mendoza-Elias ◽  
Meirigeng Qi ◽  
Tricia A. Harvat ◽  
Sang Joon Ahn ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Islet Transplantation ◽  
Mitochondrial Function ◽  
Graft Function ◽  
Complex Nature ◽  
Islet Isolation ◽  
Success Rates ◽  
Mitochondrial Integrity ◽  
Multistep Process ◽  
Underlying Mechanisms

Islet transplantation is a promising therapy for type 1 diabetes mellitus; however, success rates in achieving both short- and long-term insulin independence are not consistent, due in part to inconsistent islet quality and quantity caused by the complex nature and multistep process of islet isolation and transplantation. Since the introduction of the Edmonton Protocol in 2000, more attention has been placed on preserving mitochondrial function as increasing evidences suggest that impaired mitochondrial integrity can adversely affect clinical outcomes. Some recent studies have demonstrated that it is possible to achieve islet cytoprotection by maintaining mitochondrial function and subsequently to improve islet transplantation outcomes. However, the benefits of mitoprotection in many cases are controversial and the underlying mechanisms are unclear. This article summarizes the recent progress associated with mitochondrial cytoprotection in each step of the islet isolation and transplantation process, as well as islet potency and viability assays based on the measurement of mitochondrial integrity. In addition, we briefly discuss immunosuppression side effects on islet graft function and how transplant site selection affects islet engraftment and clinical outcomes.

scholarly journals Analysis of ATP Production Efficiency of Beat-To-Beat Calcium Fluctuations in Cardiac Mitochondria

2015 ◽  
Vol 108 (2) ◽  
pp. 109a
Author(s):  
Sangeeta Shukla ◽  
W. Jonathan Lederer ◽  
M. Saleet Jafri
Keyword(s):  
Production Efficiency ◽  
Cardiac Mitochondria ◽  
Atp Production

ATP depletion and mitochondrial functional loss during ischemia in slow and fast heart-rate hearts

1990 ◽  
Vol 259 (6) ◽  
pp. H1759-H1766 ◽  
Author(s):  
W. Rouslin ◽  
C. W. Broge ◽  
I. L. Grupp
Keyword(s):  
Mitochondrial Function ◽  
Atp Depletion ◽  
Mitochondrial Atpase ◽  
Small Contribution ◽  
Bicarbonate Buffer ◽  
Tissue Ph ◽  
Atp Production ◽  
Dog Heart ◽  
Rat Hearts

In the present study, isolated dog and rat hearts were perfused in the Langendorff mode with Krebs bicarbonate buffer in the absence and presence of 10(-5) M oligomycin. The perfusion protocols employed allowed tissue pH to drop during subsequent ischemic incubations essentially as it would in blood-perfused hearts. Tissue pH, ATP, lactate, and mitochondrial respiratory function were measured during the course of subsequent zero-flow ischemic incubations. The adenosinetriphosphatase (ATPase) activities attributable to both mitochondrial and nonmitochondrial ATPases in sonicated heart homogenates and the actomyosin ATPase in isolated cardiac myofibrils were measured in both species. Consistent with earlier results with a different model in which tissue pH was buffered during the ischemic incubations [W. Rouslin, J. L. Erickson, and R. J. Solaro. Am. J. Physiol. 250 (Heart Circ. Physiol. 19): H503-H508, 1986], the inhibition of the mitochondrial ATPase in situ by oligomycin markedly slowed both tissue ATP depletion and the loss of mitochondrial function during ischemia in the dog. However, oligomycin had only a very small and transient effect on ATP depletion and mitochondrial function in the rat. This was apparently so because of the fivefold higher rate of glycolytic ATP production as well as the nearly threefold higher total nonmitochondrial ATPase activity of ischemic rat compared with ischemic dog heart. These results suggest that although the inhibition of the mitochondrial ATPase makes a major contribution to ATP conservation in ischemic dog heart, it makes only a very small contribution in rat.

scholarly journals Phytochemicals from the Cocoa Shell Modulate Mitochondrial Function, Lipid and Glucose Metabolism in Hepatocytes via Activation of FGF21/ERK, AKT, and mTOR Pathways

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 136
Author(s):  
Miguel Rebollo-Hernanz ◽  
Yolanda Aguilera ◽  
Maria A. Martin-Cabrejas ◽  
Elvira Gonzalez de Gonzalez de Mejia
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Function ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Fatty Acid Synthase ◽  
Cell Model ◽  
Fibroblast Growth Factor 21 ◽  
Alcoholic Fatty Liver ◽  
Atp Production ◽  
Cocoa Shell

The cocoa shell is a by-product that may be revalorized as a source of bioactive compounds to prevent chronic cardiometabolic diseases. This study aimed to investigate the phytochemicals from the cocoa shell as targeted compounds for activating fibroblast growth factor 21 (FGF21) signaling and regulating non-alcoholic fatty liver disease (NAFLD)-related biomarkers linked to oxidative stress, mitochondrial function, and metabolism in hepatocytes. HepG2 cells treated with palmitic acid (PA, 500 µmol L−1) were used in an NAFLD cell model. Phytochemicals from the cocoa shell (50 µmol L−1) and an aqueous extract (CAE, 100 µg mL−1) enhanced ERK1/2 phosphorylation (1.7- to 3.3-fold) and FGF21 release (1.4- to 3.4-fold) via PPARα activation. Oxidative stress markers were reduced though Nrf-2 regulation. Mitochondrial function (mitochondrial respiration and ATP production) was protected by the PGC-1α pathway modulation. Cocoa shell phytochemicals reduced lipid accumulation (53–115%) and fatty acid synthase activity (59–93%) and prompted CPT-1 activity. Glucose uptake and glucokinase activity were enhanced, whereas glucose production and phosphoenolpyruvate carboxykinase activity were diminished. The increase in the phosphorylation of the insulin receptor, AKT, AMPKα, mTOR, and ERK1/2 conduced to the regulation of hepatic mitochondrial function and energy metabolism. For the first time, the cocoa shell phytochemicals are proved to modulate FGF21 signaling. Results demonstrate the in vitro preventive effect of the phytochemicals from the cocoa shell on NAFLD.

Low glucose and high pyruvate reduce the production of 2-oxoaldehydes, improving mitochondrial efficiency, redox regulation and stallion sperm function

2021 ◽  
Author(s):  
J M Ortiz-Rodríguez ◽  
F E Martín-Cano ◽  
G Gaitskell-Phillips ◽  
A Silva ◽  
C Ortega-Ferrusola ◽  
...  
Keyword(s):  
Redox Regulation ◽  
Krebs Cycle ◽  
Tca Cycle ◽  
Mitochondrial Activity ◽  
Atp Production ◽  
Transport Chain ◽  
Low Glucose ◽  
Mitochondrial Efficiency ◽  
Metabolic Strategies ◽  
Go Terms

Abstract Energy metabolism in spermatozoa is complex and involves the metabolism of carbohydrate fatty acids and amino acids. The ATP produced in the electron transport chain (ETC) in the mitochondria appears to be crucial for both sperm motility and maintaining viability, while glycolytic enzymes in the flagella may contribute to ATP production to sustain motility and velocity. Stallion spermatozoa seemingly use diverse metabolic strategies, and in this regard, a study of the metabolic proteome showed that gene ontology (GO) terms and Reactome pathways related to pyruvate metabolism and the Krebs cycle were predominant. Following this, the hypothesis that low glucose concentrations can provide sufficient support for motility and velocity, and thus glucose concentration can be significantly reduced in the medium, was tested. Aliquots of stallion semen in four different media were stored for 48 h at 18°C; a commercial extender containing 67 mM glucose was used as a control. Stallion spermatozoa stored in media with low glucose (1 mM) and high pyruvate (10 mM) (LG-HP) sustained better motility and velocities than those stored in the commercial extender formulated with very high glucose (61.7 ± 1.2% in INRA 96 vs 76.2 ± 1.0% in LG-HP media after 48 h of incubation at 18°C P < 0.0001). Moreover, mitochondrial activity was superior in LG-HP extenders (24.1 ± 1.8% in INRA 96 vs 51.1 ± 0.7% in LG-HP of spermatozoa with active mitochondria after 48 h of storage at 18°C P < 0.0001). Low glucose concentrations may permit more efficient sperm metabolism and redox regulation when substrates for an efficient TCA cycle are provided. The improvement seen using low glucose extenders is due to reductions in the levels of glyoxal and methylglyoxal, 2-oxoaldehydes formed during glycolysis; these compounds are potent electrophiles able to react with proteins, lipids and DNA, causing sperm damage.

Abstract 16: Progressive Alterations Of Mitochondrial Bioenergetics In The Kidney During The Development Of Salt-induced Hypertension

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Namrata Tomar ◽  
Sunil M Kandel ◽  
Xiao Zhang ◽  
Nadezhda Zheleznova ◽  
Allen W Cowley ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Complex Disease ◽  
Atp Synthesis ◽  
Control Group ◽  
Mitochondrial Uncoupling ◽  
Knock Out ◽  
Atp Production ◽  
Consumption Rates ◽  
Mitochondrial Efficiency ◽  
Salt Sensitive Hypertension

Hypertension is a complex disease and a leading cause of morbidity and mortality globally. Although oxidative stress and mitochondrial dysfunction have been found in the kidney in various models of hypertension, progressive alteration of mitochondrial oxidative phosphorylation (OxPhos) in the kidney during the development of salt-sensitive hypertension has not been characterized. The present study determined changes of OxPhos in kidneys of Dahl salt-sensitive (SS) rats before (0.4% NaCl diet; LS) and after switching to a high salt diet (4.0% NaCl; HS) during the development of hypertension. Mitochondria were isolated from the outer medulla (OM) and cortex of the kidney of SS rats fed a LS diet since weaning and studied at days 3, 7, 14 & 21 of a HS diet feeding. Oxygen consumption rates (OCR) were measured in mitochondria energized with pyruvate + malate as substrates for three different respiratory states using an Oroboros Oxygraph-2k Instrument. This includes i) leak state (in the absence of ADP), ii) ADP-stimulated state, and iii) uncoupled state (in the presence of an uncoupler FCCP). A biphasic pattern of ADP-stimulated OCR with progressive uncoupling was observed in both the renal OM and cortex. Mitochondrial efficiency for ATP synthesis was increased in the early phases of hypertension (3 & 7 days) but was severely compromised in the established phases of hypertension (14 & 21 days). This decreased mitochondrial efficiency was associated with uncoupling of OxPhos and high levels of oxidative stress which we hypothesized were due to mitochondrial ROS stimulation of membrane NOXs. To test this, experiments were performed in SS rats with double knock out (DKO) of the cytosolic subunit of NOX2 (p67 phox ) and NOX4 (SS p67phox-/-/Nox4-/- ). DKO SS rats were fed a HS diet and OCR of renal cortical and OM mitochondria was determined at days 7 and 14. In contrast to SS rats, the DKO SS rats fed a HS diet showed no significant differences in mitochondrial OCR in the cortex or OM, nor to a control group maintained on a LS diet. HS diet in SS rats initially increases the efficiency of renal cortical and medullary mitochondrial ATP production (days 1-7) followed by an enhanced ROS production with mitochondrial uncoupling and reduced efficiency of ATP production by the third week.

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