The photosensitiser azure A disrupts mitochondrial bioenergetics through intrinsic and photodynamic effects

The lack of effective disease-modifying therapeutics to tackle Alzheimer’s disease (AD) is unsettling considering the actual prevalence of this devastating neurodegenerative disorder worldwide. Intermittent hypoxic conditioning (IHC) is a powerful non-pharmacological procedure known to enhance brain resilience. In this context, the aim of the present study was to investigate the potential long-term protective impact of IHC against AD-related phenotype, putting a special focus on cognition and mitochondrial bioenergetics and dynamics. For this purpose, six-month-old male triple transgenic AD mice (3×Tg-AD) were submitted to an IHC protocol for two weeks and the behavioral assessment was performed at 8.5 months of age, while the sacrifice of mice occurred at nine months of age and their brains were removed for the remaining analyses. Interestingly, IHC was able to prevent anxiety-like behavior and memory and learning deficits and significantly reduced brain cortical levels of amyloid-β (Aβ) in 3×Tg-AD mice. Concerning brain energy metabolism, IHC caused a significant increase in brain cortical levels of glucose and a robust improvement of the mitochondrial bioenergetic profile in 3×Tg-AD mice, as mirrored by the significant increase in mitochondrial membrane potential (ΔΨm) and respiratory control ratio (RCR). Notably, the improvement of mitochondrial bioenergetics seems to result from an adaptative coordination of the distinct but intertwined aspects of the mitochondrial quality control axis. Particularly, our results indicate that IHC favors mitochondrial fusion and promotes mitochondrial biogenesis and transport and mitophagy in the brain cortex of 3×Tg-AD mice. Lastly, IHC also induced a marked reduction in synaptosomal-associated protein 25 kDa (SNAP-25) levels and a significant increase in both glutamate and GABA levels in the brain cortex of 3×Tg-AD mice, suggesting a remodeling of the synaptic microenvironment. Overall, these results demonstrate the effectiveness of the IHC paradigm in forestalling the AD-related phenotype in the 3×Tg-AD mouse model, offering new insights to AD therapy and forcing a rethink concerning the potential value of non-pharmacological interventions in clinical practice.

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S8.10 Brain mitochondrial bioenergetics is differentially affected by anesthetics fentanil and remifentanil

Biochimica et Biophysica Acta (BBA) - Bioenergetics ◽

10.1016/j.bbabio.2008.05.198 ◽

2008 ◽

Vol 1777 ◽

pp. S50

Author(s):

Sergio M. Vilela ◽

Dario L. Santos ◽

Luis M. Félix ◽

Luis M. Antunes ◽

L. José M. Almeida ◽

...

Keyword(s):

Mitochondrial Bioenergetics

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Cycling Exercise Training Enhances Platelet Mitochondrial Bioenergetics in Patients with Peripheral Arterial Disease: A Randomized Controlled Trial

Thrombosis and Haemostasis ◽

10.1055/s-0040-1722191 ◽

2021 ◽

Author(s):

Tieh-Cheng Fu ◽

Ming-Lu Lin ◽

Chih-Chin Hsu ◽

Shu-Chun Huang ◽

Yu-Ting Lin ◽

...

Keyword(s):

Exercise Training ◽

Peripheral Arterial Disease ◽

Aerobic Capacity ◽

Short Form ◽

Arterial Disease ◽

Control Group ◽

Mitochondrial Bioenergetics ◽

Cycling Exercise ◽

Complex Ii ◽

Peripheral Arterial

AbstractExercise training influences the risk of vascular thrombosis in patients with peripheral arterial disease (PAD). Mitochondrial functionalities in platelets involve the cellular bioenergetics and thrombogenesis. This study aimed to elucidate the effect of cycling exercise training (CET) on platelet mitochondrial bioenergetics in PAD patients. Forty randomly selected patients with PAD engaged in general rehabilitation (GR) with CET (i.e., cycling exercise at ventilation threshold for 30 minute/day, 3 days/week) (GR + CET, n = 20) or to a control group that only received GR course (n = 20) for 12 weeks. Systemic aerobic capacity and platelet mitochondrial bioenergetics that included oxidative phosphorylation (OXPHOS) and electron transport system (ETS) were measured using automatic gas analysis and high-resolution respirometry, respectively. The experimental results demonstrated that GR + CET for 12 weeks significantly (1) elevated VO2peak and lowered VE-VCO2 slope, (2) raised resting ankle-brachial index and enhanced cardiac output response to exercise, (3) increased the distance in 6-minute walk test and raised the Short Form-36 physical/mental component scores, and (4) enhanced capacities of mitochondrial OXPHOS and ETS in platelets by activating FADH2 (complex II)-dependent pathway. Moreover, changes in VO2peak levels were positively associated with changes in platelet OXPHOS and ETS capacities. However, no significant changes in systemic aerobic capacity, platelet mitochondrial bioenergetics, and health-related quality of life (HRQoL) occurred following GR alone. Hence, we conclude that CET effectively increases the capacities of platelet mitochondrial bioenergetics by enhancing complex II activity in patients with PAD. Moreover, the exercise regimen also enhanced functional exercise capacity, consequently improving HRQoL in PAD patients.

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O10: METFORMIN TREATMENT IMPROVES LYMPHOCYTE METABOLISM IN A MOUSE MODEL OF MAJOR SURGERY

British Journal of Surgery ◽

10.1093/bjs/znab117.010 ◽

2021 ◽

Vol 108 (Supplement_1) ◽

Author(s):

TF Jones ◽

A Gutierrez ◽

del Arroyo ◽

SM Henson ◽

GL Ackland

Keyword(s):

T Lymphocytes ◽

Mouse Model ◽

T Lymphocyte ◽

Major Surgery ◽

P Value ◽

Free Access ◽

Mitochondrial Bioenergetics ◽

Metformin Treatment ◽

Respiratory Capacity

Abstract Introduction Lymphopaenia is common after major surgery and associated with poor outcome. T-lymphocytes restrain damaging innate inflammation. Major surgery impairs T-lymphocyte metabolism in humans, which promotes lymphopaenia. Metformin is known to improve mitochondrial bioenergetics in models of inflammation. Firstly, we hypothesised that a mouse model of major surgery would demonstrate impaired T-lymphocyte metabolism and secondly, that metformin treatment in vivo would reverse the phenotype. Method Male C57Bl/6 mice aged between 8 and 12 weeks were housed in a specific pathogen free environment with free access to food and water. Animals were dosed with either vehicle (phosphate buffered saline, 20 ml/kg) or metformin (250 mg/kg) daily via intraperitoneal injection for four days prior to and after surgery. A partial hepatectomy was performed under isofluorane anaesthesia. Naive littermates were used as controls. All experiments were performed according to the Animals (Scientific Procedures) Act 1986. Splenic T-lymphocytes were isolated by negative selection using magnetic beads. Mitochondrial bioenergetics were measured using a Seahorse Extracellular Flux analyser. Parametric statistical analysis was performed and a p-value < 0.05 was chosen to represent significance. Result T-lymphocytes demonstrated reduced spare respiratory capacity (SRC, 285 vs 497 %, p=0.004) after surgery compared to naive controls. Metformin treatment in vivo reversed this observation and SRC was comparable to naive (437 vs 497 %, p=0.34). Metformin treatment in vitro increased spare respiratory capacity in T-lymphocytes from mice after surgery compared to naive (change from untreated, 187 vs 91 %, p=0.03). Conclusion Perioperative metformin treatment improved T-lymphocyte metabolism in a mouse model of major surgery. Take-home message Metformin is a potential treatment for the lymphocyte metabolic dysfunction observed after surgery.

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Sigma-1 Receptor Promotes Mitochondrial Bioenergetics by Orchestrating ER Ca2+ Leak during Early ER Stress

Metabolites ◽

10.3390/metabo11070422 ◽

2021 ◽

Vol 11 (7) ◽

pp. 422

Author(s):

Zhanat Koshenov ◽

Furkan E. Oflaz ◽

Martin Hirtl ◽

Johannes Pilic ◽

Olaf A. Bachkoenig ◽

...

Keyword(s):

Er Stress ◽

Energy Demand ◽

Molecular Mechanisms ◽

High Energy ◽

Human Neuroblastoma Cell ◽

Mitochondrial Bioenergetics ◽

Dependent Manner ◽

Human Neuroblastoma ◽

Sigma 1 Receptor ◽

Sigma 1

The endoplasmic reticulum (ER) is a complex, multifunctional organelle of eukaryotic cells and responsible for the trafficking and processing of nearly 30% of all human proteins. Any disturbance to these processes can cause ER stress, which initiates an adaptive mechanism called unfolded protein response (UPR) to restore ER functions and homeostasis. Mitochondrial ATP production is necessary to meet the high energy demand of the UPR, while the molecular mechanisms of ER to mitochondria crosstalk under such stress conditions remain mainly enigmatic. Thus, better understanding the regulation of mitochondrial bioenergetics during ER stress is essential to combat many pathologies involving ER stress, the UPR, and mitochondria. This article investigates the role of Sigma-1 Receptor (S1R), an ER chaperone, has in enhancing mitochondrial bioenergetics during early ER stress using human neuroblastoma cell lines. Our results show that inducing ER stress with tunicamycin, a known ER stressor, greatly enhances mitochondrial bioenergetics in a time- and S1R-dependent manner. This is achieved by enhanced ER Ca2+ leak directed towards mitochondria by S1R during the early phase of ER stress. Our data point to the importance of S1R in promoting mitochondrial bioenergetics and maintaining balanced H2O2 metabolism during early ER stress.

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Reviving Mitochondrial Bioenergetics: a relevant approach in epilepsy

Mitochondrion ◽

10.1016/j.mito.2021.03.009 ◽

2021 ◽

Author(s):

Shareen Singh ◽

Thakur Gurjeet Singh ◽

Ashish Kumar Rehni ◽

Vivek Sharma ◽

Manjinder Singh ◽

...

Keyword(s):

Mitochondrial Bioenergetics

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Highly sensitive H2O2 sensor based on poly(azure A)-platinum nanoparticles deposited on activated screen printed carbon electrodes

Sensors and Actuators B Chemical ◽

10.1016/j.snb.2019.126878 ◽

2019 ◽

Vol 298 ◽

pp. 126878 ◽

Cited By ~ 8

Author(s):

Rebeca Jiménez-Pérez ◽

José González-Rodríguez ◽

María-Isabel González-Sánchez ◽

Beatriz Gómez-Monedero ◽

Edelmira Valero

Keyword(s):

Platinum Nanoparticles ◽

Carbon Electrodes ◽

Azure A ◽

H2o2 Sensor ◽

Highly Sensitive ◽

Screen Printed

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Effect of fluoxetine treatment on mitochondrial bioenergetics in central and peripheral rat tissues

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2014-0462 ◽

2015 ◽

Vol 40 (6) ◽

pp. 565-574 ◽

Cited By ~ 15

Author(s):

Aline Isabel da Silva ◽

Glauber Ruda Feitoza Braz ◽

Reginaldo Silva-Filho ◽

Anderson Apolonio Pedroza ◽

Diorginis Soares Ferreira ◽

...

Keyword(s):

Skeletal Muscle ◽

Metabolic Diseases ◽

Mitochondrial Permeability Transition ◽

Permeability Transition ◽

Wistar Rat ◽

Male Rats ◽

Mitochondrial Activity ◽

Rat Tissues ◽

Transferase Activity ◽

Mitochondrial Bioenergetics

Recent investigations have focused on the mitochondrion as a direct drug target in the treatment of metabolic diseases (obesity, metabolic syndrome). Relatively few studies, however, have explicitly investigated whether drug therapies aimed at changing behavior by altering central nervous system (CNS) function affect mitochondrial bioenergetics, and none has explored their effect during early neonatal development. The present study was designed to evaluate the effects of chronic treatment of newborn male rats with the selective serotonin reuptake inhibitor fluoxetine on the mitochondrial bioenergetics of the hypothalamus and skeletal muscle during the critical nursing period of development. Male Wistar rat pups received either fluoxetine (Fx group) or vehicle solution (Ct group) from the day of birth until 21 days of age. At 60 days of age, mitochondrial bioenergetics were evaluated. The Fx group showed increased oxygen consumption in several different respiratory states and reduced production of reactive oxygen species, but there was no change in mitochondrial permeability transition pore opening or oxidative stress in either the hypothalamus or skeletal muscle. We observed an increase in glutathione S-transferase activity only in the hypothalamus of the Fx group. Taken together, our results suggest that chronic exposure to fluoxetine during the nursing phase of early rat development results in a positive modulation of mitochondrial respiration in the hypothalamus and skeletal muscle that persists into adulthood. Such long-lasting alterations in mitochondrial activity in the CNS, especially in areas regulating appetite, may contribute to permanent changes in energy balance in treated animals.

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