Mitochondrial calcium buffering depends upon temperature and is associated with hypothermic neuroprotection against hypoxia-ischemia injury.

Hypothermia (HT) is a standard of care in the management of hypoxic-ischemic brain injury (HI). However, therapeutic mechanisms of HT are not well understood. We found that at the temperature of 32°C, isolated brain mitochondria exhibited significantly greater resistance to an opening of calcium-induced permeability transition pore (mPTP), compared to 37°C.

Nucleic Acid Aptamers Increase the Anticancer Efficiency and Reduce the Toxicity of Cisplatin-Arabinogalactan Conjugates .

Cisplatin is an effective drug for treating various cancer types. However, it is highly toxic for both healthy and tumor cells. Therefore, there is a need to reduce its therapeutic dose and increase targeted bioavailability.

HIF1α stabilization in hypoxia is not oxidant-initiated.

Hypoxic adaptation mediated by HIF transcription factors requires mitochondria, which have been implicated in regulating HIF1α stability in hypoxia by distinct models that involve consuming oxygen or alternatively converting oxygen into the second messenger peroxide. Here, we use a ratiometric, peroxide reporter, HyPer to evaluate the role of peroxide in regulating HIF1α stability. We show that antioxidant enzymes are neither homeostatically induced nor are peroxide levels increased in hypoxia.

Mildronate protects heart mtDNA from oxidative stress toxicity induced by exhaustive physical exercise.

Exhaustive physical exercises are potentially dangerous for human's physical health and may lead to chronic heart disease. Therefore, individuals involved in such activity require effective and safe cardioprotectors. The goal of this research was to study Mildronate (a cardioprotective drug) effect on the level of oxidative stress markers in hearts of mice under conditions of exhausting physical exercise, such as forced swimming for 1 h per day for 7 days.

Mitochondrial Dysfunction and Permeability Transition in Neonatal Brain and Lung Injuries.

This review discusses the potential mechanistic role of abnormally elevated mitochondrial proton leak and mitochondrial bioenergetic dysfunction in the pathogenesis of neonatal brain and lung injuries associated with premature birth. Providing supporting evidence, we hypothesized that mitochondrial dysfunction contributes to postnatal alveolar developmental arrest in bronchopulmonary dysplasia (BPD) and cerebral myelination failure in diffuse white matter injury (WMI). This review also analyzes data on mitochondrial dysfunction triggered by activation of mitochondrial permeability transition pore(s) (mPTP) during the evolution of perinatal hypoxic-ischemic encephalopathy.

Metabolic ROS Signaling: To Immunity and Beyond.

Metabolism is a critical determinant of immune cell functionality. Immunometabolism, by definition, is a multidisciplinary area of immunology research that integrates the knowledge of energy transduction mechanisms and biochemical pathways. An important concept in the field is metabolic switch, a transition of immune cells upon activation to preferential utilization of select catabolic pathways for their energy needs.

p62-Nrf2-p62 Mitophagy Regulatory Loop as a Target for Preventive Therapy of Neurodegenerative Diseases.

Turnover of the mitochondrial pool due to coordinated processes of mitochondrial biogenesis and mitophagy is an important process in maintaining mitochondrial stability. An important role in this process is played by the Nrf2/ARE signaling pathway, which is involved in the regulation of the expression of genes responsible for oxidative stress protection, regulation of mitochondrial biogenesis, and mitophagy. The p62 protein is a multifunctional cytoplasmic protein that functions as a selective mitophagy receptor for the degradation of ubiquitinated substrates.

Pulse Shape Effects in Electrocaloric Cooling.

We report on the solution of the heat equation, which describes the electrocaloric effect in a ferroelectric layer. The dependence of the heat flux at the layer interface and the thermodynamic efficiency on the shape and frequency of the applied pulse is investigated. According to the calculations, the dependence of the efficiency on the frequency for a rectangular and sinusoidal pulse has a markedly different character.

Method for detection of mtDNA damages for evaluating of pesticides toxicity for bumblebees (Bombus terrestris L.).

Bumblebees are important for crop pollination. Currently, the number of pollinators is decreasing worldwide, which is attributed mostly to the widespread use of pesticides. The aim of this work was to develop a method for assessing the genotoxicity of pesticides for the Bombus terrestris L.

Lung cancer increases HO concentration in the exhaled breath condensate, extent of mtDNA damage, and mtDNA copy number in buccal mucosa.

We have shown that the HO concentration in exhaled breath condensate (EBC) in lung cancer patients increases significantly compared to the EBC of healthy people and revealed the correlation between the HO level in the EBC and amount of mtDNA damage in buccal mucosa cells. The HO hyper-production may trigger mitochondrial biogenesis, thereby resulting in an increase in mtDNA copy number. However, we did not observe a significant difference in the studied parameters between smokers and non-smokers.

Crosstalk between the mTOR and Nrf2/ARE signaling pathways as a target in the improvement of long-term potentiation.

In recent years, a significant progress was made in understanding molecular mechanisms of long-term memory. Long-term memory formation requires strengthening of neuronal connections (LTP, long-term potentiation) associated with structural rearrangement of neurons. The key role in the synthesis of proteins essential for these rearrangements belong to mTOR (mammalian target of rapamycin) complexes and signaling pathways involved in mTOR regulation.

Unique features of flight muscles mitochondria of honey bees (Apis mellifera L.).

Honey bees Apis mellifera L. are one of the most studied insect species due to their economic importance. The interest in studying honey bees chiefly stems from the recent rapid decrease in their world population, which has become a problem of food security.

Autophagy Induction by Bexarotene Promotes Mitophagy in Presenilin 1 Familial Alzheimer's Disease iPSC-Derived Neural Stem Cells.

Adult neurogenesis defects have been demonstrated in the brains of Alzheimer's disease (AD) patients. The neurogenesis impairment is an early critical event in the course of familiar AD (FAD) associated with neuronal loss. It was suggested that neurologic dysfunction in AD may be caused by impaired functioning of hippocampal neural stem cells (NSCs).

Redox-Dependent Loss of Flavin by Mitochondrial Complex I in Brain Ischemia/Reperfusion Injury.

Brain ischemia/reperfusion (I/R) is associated with impairment of mitochondrial function. However, the mechanisms of mitochondrial failure are not fully understood. This work was undertaken to determine the mechanisms and time course of mitochondrial energy dysfunction after reperfusion following neonatal brain hypoxia-ischemia (HI) in mice.

Methylene blue does not bypass Complex III antimycin block in mouse brain mitochondria.

Methylene blue (MB) is a promising prodrug to treat mitochondrial dysfunctions that is currently being used in clinical trials for Alzheimer's disease. MB can penetrate the blood brain barrier, accumulating in brain mitochondria where it acts as a redox mediator in the electron transfer chain (ETC). Mitochondrial flavins are thought to reduce MB, which is then oxidized by cytochrome c, thereby bypassing inhibited Complex I of ETC.

Benfotiamine treatment activates the Nrf2/ARE pathway and is neuroprotective in a transgenic mouse model of tauopathy.

Impaired glucose metabolism, decreased levels of thiamine and its phosphate esters, and reduced activity of thiamine-dependent enzymes, such as pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase and transketolase occur in Alzheimer's disease (AD). Thiamine deficiency exacerbates amyloid beta (Aβ) deposition, tau hyperphosphorylation and oxidative stress. Benfotiamine (BFT) rescued cognitive deficits and reduced Aβ burden in amyloid precursor protein (APP)/PS1 mice.

Prohibitin is a positive modulator of mitochondrial function in PC12 cells under oxidative stress.

Prohibitin (PHB) is a ubiquitously expressed and evolutionarily conserved mitochondrial protein with multiple functions. We have recently shown that PHB up-regulation offers robust protection against neuronal injury in models of cerebral ischemia in vitro and in vivo, but the mechanism by which PHB affords neuroprotection remains to be elucidated. Here, we manipulated PHB expression in PC12 neural cells to investigate its impact on mitochondrial function and the mechanisms whereby it protects cells exposed to oxidative stress.

β-Guanidinopropionic Acid Stimulates Brain Mitochondria Biogenesis and Alters Cognitive Behavior in Nondiseased Mid-Age Mice.

β-guanidinopropionic acid (β-GPA) has been used as a nutritional supplement for increasing physical strength and endurance with positive and predictable results. In muscles, it works as a nonadaptive stimulator of mitochondria biogenesis; it also increases lipid metabolism. There are data indicating that β-GPA can be also neuroprotective, but its mechanisms of action in the brain are less understood.

Estrogen receptor beta modulates permeability transition in brain mitochondria.

Recent evidence highlights a role for sex and hormonal status in regulating cellular responses to ischemic brain injury and neurodegeneration. A key pathological event in ischemic brain injury is the opening of a mitochondrial permeability transition pore (MPT) induced by excitotoxic calcium levels, which can trigger irreversible damage to mitochondria accompanied by the release of pro-apoptotic factors. However, sex differences in brain MPT modulation have not yet been explored.

Krebs cycle metabolites and preferential succinate oxidation following neonatal hypoxic-ischemic brain injury in mice.

BackgroundReverse electron transport (RET) driven by the oxidation of succinate has been proposed as the mechanism of accelerated production of reactive oxygen species (ROS) in post-ischemic mitochondria. However, it remains unclear whether upon reperfusion, mitochondria preferentially oxidase succinate.MethodsNeonatal mice were subjected to Rice-Vannucci model of hypoxic-ischemic brain injury (HI) followed by assessment of Krebs cycle metabolites, mitochondrial substrate preference, and HO generation rate in the ischemic brain.

Reverse electron transfer results in a loss of flavin from mitochondrial complex I: Potential mechanism for brain ischemia reperfusion injury.

Ischemic stroke is one of the most prevalent sources of disability in the world. The major brain tissue damage takes place upon the reperfusion of ischemic tissue. Energy failure due to alterations in mitochondrial metabolism and elevated production of reactive oxygen species (ROS) is one of the main causes of brain ischemia-reperfusion (IR) damage.

Distinct intracellular sAC-cAMP domains regulate ER Ca signaling and OXPHOS function.

cAMP regulates a wide variety of physiological functions in mammals. This single second messenger can regulate multiple, seemingly disparate functions within independently regulated cell compartments. We have previously identified one such compartment inside the matrix of the mitochondria, where soluble adenylyl cyclase (sAC) regulates oxidative phosphorylation (OXPHOS).

Mild metabolic perturbations alter succinylation of mitochondrial proteins.

Succinylation of proteins is widespread, modifies both the charge and size of the molecules, and can alter their function. For example, liver mitochondrial proteins have 1,190 unique succinylation sites representing multiple metabolic pathways. Succinylation is sensitive to both increases and decreases of the NAD -dependent desuccinylase, SIRT5.

Mutant TDP-43 does not impair mitochondrial bioenergetics in vitro and in vivo.

Background: Mitochondrial dysfunction has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Functional studies of mitochondrial bioenergetics have focused mostly on superoxide dismutase 1 (SOD1) mutants, and showed that mutant human SOD1 impairs mitochondrial oxidative phosphorylation, calcium homeostasis, and dynamics. However, recent reports have indicated that alterations in transactivation response element DNA-binding protein 43 (TDP-43) can also lead to defects of mitochondrial morphology and dynamics.