Mitochondrial calcium cycling in neuronal function and neurodegeneration

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Jan. 24, 2023

Mitochondria are essential for proper cellular function through their critical roles in ATP synthesis, reactive oxygen species production, calcium (Ca

Language: Английский

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Mitochondrial Ca2+ handling as a cell signaling hub: lessons from astrocyte function

Essays in Biochemistry, Journal Year: 2023, Volume and Issue: 67(1), P. 63 - 75

Published: Jan. 13, 2023

Abstract Astrocytes are a heterogenous population of macroglial cells spread throughout the central nervous system with diverse functions, expression signatures, and intricate morphologies. Their subcellular compartments contain distinct range mitochondria, functional microdomains exhibiting widespread activities, such as controlling local metabolism Ca2+ signaling. is an ion utmost importance, both physiologically pathologically, participates in critical processes, including synaptic plasticity, neuron–astrocyte integration, excitotoxicity, mitochondrial physiology metabolism. The handling formed by uniporter complex (MCUc), which mediates influx, Na+/Ca2+ exchanger (NCLX), responsible for most efflux, well additional components, permeability transition pore (mtPTP). Over last decades, has been shown to be key brain homeostasis, acting centrally physiopathological processes astrogliosis, astrocyte–neuron activity energy control, neurodegeneration. In this review, we discuss current state knowledge regarding molecular composition, highlighting its impact on astrocytic homeostasis.

Language: Английский

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The great astroglial metabolic revolution: Mitochondria fuel astrocyte homeostatic support and neuroprotection

Cell Calcium, Journal Year: 2022, Volume and Issue: 104, P. 102583 - 102583

Published: April 1, 2022

Language: Английский

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Mild Traumatic Brain Injury Induces Mitochondrial Calcium Overload and Triggers the Upregulation of NCLX in the Hippocampus

Antioxidants, Journal Year: 2023, Volume and Issue: 12(2), P. 403 - 403

Published: Feb. 7, 2023

Traumatic brain injury (TBI) is damage due to external forces. Mild TBI (mTBI) the most common form of TBI, and repeated mTBI a risk factor for developing neurodegenerative diseases. Several mechanisms neuronal have been described in cortex hippocampus, including mitochondrial dysfunction. However, up until now, there no studies evaluating calcium dynamics. Here, we evaluated dynamics an model mice using isolated hippocampal mitochondria biochemical studies. We observed that 24 h after mTBI, decrease membrane potential increase basal matrix levels. These findings are accompanied by increased efflux changes uptake. also NCLX protein levels retention capacity. Our results suggest under cells respond incrementing restore function.

Language: Английский

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Mitochondrial calcium signaling in non-neuronal cells: Implications for Alzheimer's disease pathogenesis

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1870(5), P. 167169 - 167169

Published: April 15, 2024

Language: Английский

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Early Synapse-Specific Alterations of Photoreceptor Mitochondria in the EAE Mouse Model of Multiple Sclerosis

Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 206 - 206

Published: Jan. 30, 2025

Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system (CNS) linked to many neurological disabilities. The visual frequently impaired in MS. In previous studies, we observed early malfunctions rod photoreceptor ribbon synapses EAE mouse model MS that included alterations synaptic vesicle cycling and disturbances presynaptic Ca2+ homeostasis. Since these events are highly energy-demanding, analyzed whether mitochondria, which play a major role energy metabolism, might be involved at stage. Rod terminals contain single large mitochondrion next ribbon. present study, expression functionally relevant mitochondrial proteins (MIC60, ATP5B, COX1, PINK1, DRP1) by high-resolution qualitative quantitative immunofluorescence microscopy, immunogold electron microscopy Western blot experiments. We decreased mitochondria photoreceptors stage, suggesting dysfunctions important synapse pathology. Interestingly, were strongly compromised EAE, whereas extra-synaptic inner segments remained unchanged, demonstrating functional heterogeneity mitochondria.

Language: Английский

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Mitochondrial sodium/calcium exchanger NCLX regulates glycolysis in astrocytes, impacting on cognitive performance

Journal of Neurochemistry, Journal Year: 2022, Volume and Issue: 165(4), P. 521 - 535

Published: Dec. 23, 2022

Intracellular Ca

Language: Английский

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Regulation of Aging and Longevity by Ion Channels and Transporters

Cells, Journal Year: 2022, Volume and Issue: 11(7), P. 1180 - 1180

Published: March 31, 2022

Despite significant advances in our understanding of the mechanisms that underlie age-related physiological decline, ability to translate these insights into actionable strategies extend human healthspan has been limited. One major reasons for existence this barrier is with a few important exceptions, many proteins mediate aging have proven be undruggable. The argument put forth here amenability ion channels and transporters pharmacological manipulation could leveraged develop novel therapeutic combat aging. This review delves established roles regulation longevity via their influence on membrane excitability, Ca2+ homeostasis, mitochondrial endolysosomal function, transduction sensory stimuli. goal provide reader an emergent themes, prompt further investigation how activities sculpt trajectories cellular organismal

Language: Английский

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Mitochondrial Ca²⁺efflux controls neuronal metabolism and long-term memory across species

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 1, 2024

Abstract While impairing neuronal metabolism limits brain performance, it remains poorly understood whether enhancing in neurons, contrast, could boost function. We find that reducing the expression of mitochondrial H + /Ca 2+ exchanger Letm1 results increased Ca retention matrix firing which overactivates flies and rodents. upscaled metabolic states active neurons central memory circuits mice enable storing long-term memories training paradigms wild-type counterparts both species fail to remember. Our findings unveil an evolutionarily conserved mechanism controls prove its crucial role governing higher functions, such as formation. Highlights - activity-driven efflux Increased during activity Activity-driven upscaling facilitates olfactory

Language: Английский

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Targeting mitochondrial Ca²⁺ uptake for the treatment of amyotrophic lateral sclerosis

The Journal of Physiology, Journal Year: 2023, Volume and Issue: 602(8), P. 1519 - 1549

Published: Nov. 27, 2023

Amyotrophic lateral sclerosis (ALS) is a rare adult-onset neurodegenerative disease characterized by progressive motor neuron (MN) loss, muscle denervation and paralysis. Over the past several decades, researchers have made tremendous efforts to understand pathogenic mechanisms underpinning ALS, with much yet be resolved. ALS described as non-cell autonomous condition pathology detected in both MNs non-neuronal cells, such glial cells skeletal muscle. Studies patient animal models reveal ubiquitous abnormalities mitochondrial structure function, disturbance of intracellular calcium homeostasis various tissue types, suggesting pivotal role aberrant uptake dysfunctional signalling cascades pathogenesis. Calcium dysfunction are intricately related manifestation cell death contributing MN loss dysfunction. In this review, we discuss potential contribution signalling, particularly uptake, Functional consequences excessive possible therapeutic strategies targeting or uniporter, main channel mediating influx, also discussed.

Language: Английский

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