Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by neuronal dysfunction leading to decreased memory and cognitive function. AD research has largely focused on the potential pathogenic role of two disease hallmarks: amyloid beta and phosphorylated tau. However, pharmacological interventions targeting these disease hallmarks have met with limited clinical trial success.

Interactive effects of temperature, cadmium, and hypoxia on rainbow trout (Oncorhynchus mykiss) liver mitochondrial bioenergetics.

Fish in their natural environments possess elaborate mechanisms that regulate physiological function to mitigate the adverse effects of multiple environmental stressors such as temperature, metals, and hypoxia. We investigated how warm acclimation affects mitochondrial responses to Cd, hypoxia, and acute temperature shifts (heat shock and cold snap) in rainbow trout. We observed that state 3 respiration driven by complex I (CI) was resistant to the stressors while warm acclimation and Cd reduced complex I +II (CI + II) driven state 3 respiration.

DMT1 knockout abolishes ferroptosis induced mitochondrial dysfunction in C. elegans amyloid β proteotoxicity.

Iron is critical for neuronal activity and metabolism, and iron dysregulation alters these functions in age-related neurodegenerative disorders, such as Alzheimer's disease (AD). AD is a chronic neurodegenerative disease characterized by progressive neuronal dysfunction, memory loss and decreased cognitive function. AD patients exhibit elevated iron levels in the brain compared to age-matched non-AD individuals.

DMT1 knockout abolishes ferroptosis induced mitochondrial dysfunction in amyloid β proteotoxicity.

Iron is critical for neuronal activity and metabolism, and iron dysregulation alters these functions in age-related neurodegenerative disorders, such as Alzheimer's disease (AD). AD is a chronic neurodegenerative disease characterized by progressive neuronal dysfunction, memory loss and decreased cognitive function. AD patients exhibit elevated iron levels in the brain compared to age-matched non-AD individuals.

Interactive effects of temperature, cadmium, and hypoxia on rainbow trout liver mitochondrial bioenergetics.

Fish in their natural environments possess elaborate mechanisms that regulate physiological function to mitigate the adverse effects of multiple environmental stressors such as temperature, metals, and hypoxia. We investigated how warm acclimation affects mitochondrial responses to Cd, hypoxia, and acute temperature shifts (heat shock and cold snap) in rainbow trout. We observed that state 3 respiration driven by complex I (CI) was resistant to the stressors while warm acclimation and Cd reduced complex I +II (CI + II) driven state 3 respiration.

Epigenetic erosion of H4K20me1 induced by inflammation drives aged stem cell ferroptosis.

Aging is associated with a decline in stem cell functionality and number across the organism. In this study, we aimed to further unravel Muscle Stem Cells (MuSCs) aging by assessing how systemic factors influence MuSC fate decisions through long-term epigenetic landscape remodelling. As aging is intricately linked to a pro-inflammatory shift, we studied the epigenetic effects of inflammatory signals in MuSCs and measured decreased H4K20me1 levels.

Osmo-respiratory compromise in the mosshead sculpin (Clinocottus globiceps): effects of temperature, hypoxia, and re-oxygenation on rates of diffusive water flux and oxygen uptake.

In nature, mosshead sculpins (Clinocottus globiceps) are challenged by fluctuations in temperature and oxygen levels in their environment. However, it is unclear how mosshead sculpins modulate the permeability of their branchial epithelia to water and O in response to temperature or hypoxia stress. Acute decrease in temperature from 13 to 6 C reduced diffusive water flux rate by 22% and ṀO by 51%, whereas acute increase in temperature from 13 to 25 C increased diffusive water flux rate by 217% and ṀO by 140%, yielding overall Q values of 2.

The Caenorhabditis elegans innexin INX-20 regulates nociceptive behavioral sensitivity.

Organisms rely on chemical cues in their environment to indicate the presence or absence of food, reproductive partners, predators, or other harmful stimuli. In the nematode Caenorhabditis elegans, the bilaterally symmetric pair of ASH sensory neurons serves as the primary nociceptors. ASH activation by aversive stimuli leads to backward locomotion and stimulus avoidance.

A reversible mitochondrial complex I thiol switch mediates hypoxic avoidance behavior in C. elegans.

C. elegans react to metabolic distress caused by mismatches in oxygen and energy status via distinct behavioral responses. At the molecular level, these responses are coordinated by under-characterized, redox-sensitive processes, thought to initiate in mitochondria.

Iron Dysregulation in Mitochondrial Dysfunction and Alzheimer's Disease.

Alzheimer's disease (AD) is a devastating progressive neurodegenerative disease characterized by neuronal dysfunction, and decreased memory and cognitive function. Iron is critical for neuronal activity, neurotransmitter biosynthesis, and energy homeostasis. Iron accumulation occurs in AD and results in neuronal dysfunction through activation of multifactorial mechanisms.

Reverse translation: effects of acclimation temperature and acute temperature challenges on oxygen consumption, diffusive water flux, net sodium loss rates, Q values and mass scaling coefficients in the rainbow trout (Oncorhynchus mykiss).

Our understanding is limited on how fish adjust the effective permeability of their branchial epithelium to ions and water while altering O uptake rate (MO) with acute and chronic changes in temperature. We investigated the effects of acclimation temperature (8 °C, 13 °C and 18 °C) and acute temperature challenges [acute rise (acclimated at 8 °C, measured at 13 °C and 18 °C), acute drop (acclimated at 18 °C, measured at 8 °C and 13 °C) and intermediate (acclimated at 13 °C, measured at 8 °C and 18 °C)] on routine MO, diffusive water flux, and net sodium loss rates in 24-h fasted rainbow trout (Oncorhynchus mykiss). In the temperature challenge tests, measurements were made during the first hour.

Physiologic Implications of Reactive Oxygen Species Production by Mitochondrial Complex I Reverse Electron Transport.

Mitochondrial reactive oxygen species (ROS) can be either detrimental or beneficial depending on the amount, duration, and location of their production. Mitochondrial complex I is a component of the electron transport chain and transfers electrons from NADH to ubiquinone. Complex I is also a source of ROS production.

The osmorespiratory compromise in rainbow trout (Oncorhynchus mykiss): The effects of fish size, hypoxia, temperature and strenuous exercise on gill diffusive water fluxes and sodium net loss rates.

In the context of the osmorespiratory compromise, hypoxia and temperature have been little studied relative to exercise, and diffusive water flux rates (as assessed by HO efflux) have received almost no attention. We investigated the effects of fish size, hypoxia, exercise and acute temperature increase on diffusive water flux rates and net sodium loss rates in juvenile rainbow trout. Trout weighing 13-50 g were used to determine the effects of fish size under normoxia.

Combined effects of cadmium, temperature and hypoxia-reoxygenation on mitochondrial function in rainbow trout (Oncorhynchus mykiss).

Although aquatic organisms face multiple environmental stressors that may interact to alter adverse outcomes, our knowledge of stressor-stressor interaction on cellular function is limited. We investigated the combined effects of cadmium (Cd), hypoxia-reoxygenation (H-R) and temperature on mitochondrial function. Liver mitochondria from juvenile rainbow trout were exposed to Cd (0-20μM) and H-R (0 and 5min) at 5, 13 and 25°C followed by measurements of mitochondrial Cd load, volume, complex І active (A)↔deactive (D) transition, membrane potential, ROS release and ultrastructural changes.

Hypoxia-reoxygenation differentially alters the thermal sensitivity of complex I basal and maximal mitochondrial oxidative capacity.

Hypoxia-reoxygenation (H-R) transitions and temperature fluctuations occur frequently in biological systems and likely interact to alter cell function. To test how H-R modulates mitochondrial function at different temperatures we measured the effects of H-R on isolated fish liver mitochondrial oxidation rates over a wide temperature range (5-25°C). Subsequently, the mechanisms underlying H-R induced mitochondrial responses were examined.

Bioenergetic and volume regulatory effects of mitoKATP channel modulators protect against hypoxia-reoxygenation-induced mitochondrial dysfunction.

The mitochondrial ATP-sensitive K(+) (mitoKATP) channel plays a significant role in mitochondrial physiology and protects against ischemic reperfusion injury in mammals. Although fish frequently face oxygen fluctuations in their environment, the role of the mitoKATP channel in regulating the responses to oxygen stress is rarely investigated in this class of animals. To elucidate whether and how the mitoKATP channel protects against hypoxia-reoxygenation (H-R)-induced mitochondrial dysfunction in fish, we first determined the mitochondrial bioenergetic effects of two key modulators of the channel, diazoxide and 5-hydroxydecanoate (5-HD), using a wide range of doses.

Effects of hypoxia-cadmium interactions on rainbow trout (Oncorhynchus mykiss) mitochondrial bioenergetics: attenuation of hypoxia-induced proton leak by low doses of cadmium.

The goal of the present study was to elucidate the modulatory effects of cadmium (Cd) on hypoxia/reoxygenation-induced mitochondrial dysfunction in light of the limited understanding of the mechanisms of multiple stressor interactions in aquatic organisms. Rainbow trout (Oncorhynchus mykiss) liver mitochondria were isolated and energized with complex I substrates (malate-glutamate), and exposed to hypoxia (0>PO2<2 Torr) for 0-60 min followed by reoxygenation and measurement of coupled and uncoupled respiration and complex I enzyme activity. Thereafter, 5 min hypoxia was used to probe interactions with Cd (0-20 μmol l(-1)) and to test the hypothesis that deleterious effects of hypoxia/reoxygenation on mitochondria were mediated by reactive oxygen species (ROS).