Mitochondrial Glutathione in Cellular Redox Homeostasis and Disease Manifestation

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1314 - 1314

Published: Jan. 21, 2024

Mitochondria are critical for providing energy to maintain cell viability. Oxidative phosphorylation involves the transfer of electrons from substrates oxygen produce adenosine triphosphate. also regulate proliferation, metastasis, and deterioration. The flow in mitochondrial respiratory chain generates reactive species (ROS), which harmful cells at high levels. stress caused by ROS accumulation has been associated with an increased risk cancer, cardiovascular liver diseases. Glutathione (GSH) is abundant cellular antioxidant that primarily synthesized cytoplasm delivered mitochondria. Mitochondrial glutathione (mGSH) metabolizes hydrogen peroxide within A long-term imbalance ratio mGSH can cause dysfunction, apoptosis, necroptosis, ferroptosis, may lead disease. This study aimed review physiological functions, anabolism, variations organ tissue accumulation, delivery GSH mitochondria relationships between levels, GSH/GSH disulfide (GSSG) ratio, programmed death, ferroptosis. We discuss diseases deficiency related therapeutics.

Language: Английский

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Mitochondrial dysfunction in long COVID: mechanisms, consequences, and potential therapeutic approaches

GeroScience, Journal Year: 2024, Volume and Issue: 46(5), P. 5267 - 5286

Published: April 26, 2024

Abstract The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has introduced medical community to phenomenon of long COVID, a condition characterized persistent symptoms following resolution acute phase infection. Among myriad reported COVID sufferers, chronic fatigue, cognitive disturbances, and exercise intolerance are predominant, suggesting systemic alterations beyond initial viral pathology. Emerging evidence pointed mitochondrial dysfunction as potential underpinning mechanism contributing persistence diversity symptoms. This review aims synthesize current findings related in exploring its implications for cellular energy deficits, oxidative stress, immune dysregulation, metabolic endothelial dysfunction. Through comprehensive analysis literature, we highlight significance health pathophysiology drawing parallels with similar clinical syndromes linked post-infectious states other diseases where impairment been implicated. We discuss therapeutic strategies targeting function, including pharmacological interventions, lifestyle modifications, exercise, dietary approaches, emphasize need further research collaborative efforts advance our understanding management COVID. underscores critical role calls multidisciplinary approach address gaps knowledge treatment options those affected this condition.

Language: Английский

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Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(1), P. 574 - 574

Published: Jan. 1, 2024

Post-viral fatigue syndrome (PVFS) encompasses a wide range of complex neuroimmune disorders unknown causes characterised by disabling post-exertional fatigue, myalgia and joint pain, cognitive impairments, unrefreshing sleep, autonomic dysfunction, neuropsychiatric symptoms. It includes myalgic encephalomyelitis, also known as chronic (ME/CFS); fibromyalgia (FM); more recently post-COVID-19 condition (long COVID). To date, there are no definitive clinical case criteria FDA-approved pharmacological therapies for PVFS. Given the current lack effective treatments, is need to develop novel therapeutic strategies these disorders. Mitochondria, cellular organelles responsible tissue energy production, have garnered attention in research into PVFS due their crucial role bioenergetic metabolism conditions. The accumulating literature has identified link between mitochondrial dysfunction low-grade systemic inflammation ME/CFS, FM, long COVID. address this issue, article aims critically review evidence relating pathogenesis disorders; particular, it evaluate effectiveness coenzyme Q10 supplementation on pain symptoms strategy treatment

Language: Английский

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Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

npj Science of Food, Journal Year: 2024, Volume and Issue: 8(1)

Published: March 30, 2024

Language: Английский

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Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(1), P. 364 - 364

Published: Jan. 3, 2025

This review describes our current understanding of the role mitochondria in repurposing anti-diabetes drugs metformin, gliclazide, GLP-1 receptor agonists, and SGLT2 inhibitors for additional clinical benefits regarding unhealthy aging, long COVID, mental neurogenerative disorders, obesity. Metformin, most prominent these diabetes drugs, has been called “Drug Miracles Wonders,” as trials have found it to be beneficial human patients suffering from maladies. To promote viral replication all infected cells, SARS-CoV-2 stimulates liver cells produce glucose export into blood stream, which can cause COVID patients, reduces levels blood, was shown cut incidence rate half recovering SARS-CoV-2. Metformin leads phosphorylation AMP-activated protein kinase AMPK, accelerates import via transporter GLUT4 switches starvation mode, counteracting virus. Diabetes also stimulate unfolded response thus mitophagy, is healthy aging health. were mimic exercise help reduce body weight.

Language: Английский

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Host mitochondria: more than an organelle in SARS-CoV-2 infection

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Aug. 25, 2023

Since December 2019, the world has been facing viral pandemic called COVID-19 (Coronavirus disease 2019) caused by a new beta-coronavirus named severe acute respiratory syndrome coronavirus-2, or SARS-CoV-2. patients may present with wide range of symptoms, from asymptomatic to requiring intensive care support. The form is often marked an altered immune response and cytokine storm. Advanced age, age-related underlying diseases, including metabolic syndromes, appear contribute increased severity mortality suggesting role for mitochondria in pathogenesis. Furthermore, since system associated its damage-related molecular patterns (mtDAMPs), host mitochondrial play important during infections. Viruses have evolved modulate function survival proliferation, which turn could lead cellular stress progression. Recent studies focused on possible roles SARS-CoV-2 infection. It suggested that hijacking be key factor In this review, we discuss infections infection based past knowledge. Paying attention will help better understand pathophysiology achieve effective methods prevention, diagnosis, treatment.

Language: Английский

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Mitochondrial oxidative stress, mitochondrial ROS storms in long COVID pathogenesis

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Dec. 22, 2023

Significance This review discusses the coronavirus disease 2019 (COVID-19) pathophysiology in context of diabetes and intracellular reactions by COVID-19, including mitochondrial oxidative stress storms, ROS long COVID. Recent advances The COVID is suffered ~10% COVID-19 patients. Even virus does not exist, patients suffer for even over a year, could be mitochondria dysregulation disease. Critical issues Patients who recover from can develop new or persistent symptoms multi-organ complications lasting weeks months, called underlying mechanisms involved still unclear. Once persist, they cause significant damage, leading to numerous, symptoms. Future directions A comprehensive map stages pathogenetic related effective drugs treat prevent it are required, which will aid development future treatments symptom relief.

Language: Английский

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Mitochondrial dynamics and psychiatric disorders: The missing link

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 165, P. 105837 - 105837

Published: July 30, 2024

Language: Английский

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Induction of the Inflammasome by the SARS‐CoV‐2 Accessory Protein ORF9b, Abrogated by Small‐Molecule ORF9b Homodimerization Inhibitors

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(2)

Published: Feb. 1, 2025

ABSTRACT Viral accessory proteins play critical roles in viral escape from host innate immune responses and inflammatory pathogenesis. Here we show that the SARS‐CoV‐2 protein, ORF9b, but not other (ORF3a, ORF3b, ORF6, ORF7, ORF8, ORF9c, ORF10), strongly activates inflammasome‐dependent caspase‐1 A549 lung carcinoma cells THP‐1 monocyte‐macrophage cells. Exposure to lipopolysaccharide (LPS) ATP additively enhanced activation of by suggesting ORF9b LPS follow parallel pathways inflammasome caspase‐1. Following rational silico approaches, have designed small molecules capable inhibiting homodimerization which experimentally inhibited ORF9b‐ORF9b homotypic interactions, caused mitochondrial eviction ORF9b‐induced cells, cytokine release restored type I interferon (IFN‐I) signaling suppressed both cell models. These are first‐in‐class compounds targeting a protein for viral‐induced exacerbated inflammation responses, with potential mitigating severe immunopathogenic damage induced highly pathogenic coronaviruses restoring antiviral curtailed infection.

Language: Английский

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Genetic Landscape and Mitochondrial Metabolic Dysregulation in Patients Suffering From Severe Long COVID

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(3)

Published: March 1, 2025

ABSTRACT Long COVID represents a significant global health challenge with an unclear etiology. Alongside accumulating evidence of mitochondrial dysfunction in patients acute SARS‐CoV‐2 infection, symptomatic overlap exists between long and disorders. However, the genetic underpinnings have not been previously explored. We employed whole genome sequencing to analyze 13 severe identify defects related function. performed extracellular bioenergetics flux analysis on peripheral blood mononuclear cells proteomics evaluate cellular compared results those healthy controls. Our investigation identified 10 variants classified as pathogenic or likely 83 unknown significance affecting wide range mitochondria‐associated biological functions. Bioenergetics revealed altered ATP production rate four This study presents initial potential underlying predisposition while demonstrating energy capacity subset these patients. These findings open avenues for further research into role pathology suffering from may pave way targeted therapeutic strategies aimed at mitigating dysfunction.

Language: Английский

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