Mitochondria and Brain Disease: A Comprehensive Review of Pathological Mechanisms and Therapeutic Opportunities

Biomedicines, Journal Year: 2023, Volume and Issue: 11(9), P. 2488 - 2488

Published: Sept. 7, 2023

Mitochondria play a vital role in maintaining cellular energy homeostasis, regulating apoptosis, and controlling redox signaling. Dysfunction of mitochondria has been implicated the pathogenesis various brain diseases, including neurodegenerative disorders, stroke, psychiatric illnesses. This review paper provides comprehensive overview intricate relationship between disease, focusing on underlying pathological mechanisms exploring potential therapeutic opportunities. The covers key topics such as mitochondrial DNA mutations, impaired oxidative phosphorylation, dynamics, calcium dysregulation, reactive oxygen species generation context disease. Additionally, it discusses emerging strategies targeting dysfunction, protective agents, metabolic modulators, gene therapy approaches. By critically analysing existing literature recent advancements, this aims to enhance our understanding multifaceted disease shed light novel interventions.

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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KCNK1 promotes proliferation and metastasis of breast cancer cells by activating lactate dehydrogenase A (LDHA) and up-regulating H3K18 lactylation

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(6), P. e3002666 - e3002666

Published: June 21, 2024

Breast cancer is the most prevalent malignancy and significant contributor to mortality in female oncology patients. Potassium Two Pore Domain Channel Subfamily K Member 1 (KCNK1) differentially expressed a variety of tumors, but mechanism its function breast unknown. In this study, we found for first time that KCNK1 was significantly up-regulated human correlated with poor prognosis promoted proliferation, invasion, metastasis vitro vivo. Further studies unexpectedly revealed increased glycolysis lactate production cells by binding activating dehydrogenase A (LDHA), which histones lysine lactylation induce expression series downstream genes LDHA itself. Notably, served as vicious positive feedback reduce tumor cell stiffness adhesion, eventually resulted cancer. conclusion, our results suggest may serve potential biomarker, deeper insight into cancer-promoting uncover novel therapeutic target treatment.

Language: Английский

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The Vicious Cycle of Type 2 Diabetes Mellitus and Skeletal Muscle Atrophy: Clinical, Biochemical, and Nutritional Bases

Nutrients, Journal Year: 2024, Volume and Issue: 16(1), P. 172 - 172

Published: Jan. 4, 2024

Today, type 2 diabetes mellitus (T2DM) and skeletal muscle atrophy (SMA) have become increasingly common occurrences. Whether the onset of T2DM increases risk SMA or vice versa has long been under investigation. Both conditions are associated with negative changes in health, which can, turn, lead to impaired physical function, a lowered quality life, an increased mortality. Poor nutrition can exacerbate both SMA. linked by vicious cycle events that reinforce worsen each other. Muscle insulin resistance appears be pathophysiological link between To explore this association, our review (i) compiles evidence on clinical association SMA, (ii) reviews mechanisms underlying biochemical muscles people at (iii) examines how nutritional therapy activity as muscle-targeted treatments benefit population. Based evidence, we conclude effective treatment patients T2DM-SMA depends restoration maintenance mass. We thus propose regular intake key functional nutrients, along guidance for activity, help maintain euglycemia improve status all

Language: Английский

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Mitochondrial dysfunction at the crossroad of cardiovascular diseases and cancer

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Sept. 19, 2023

A large body of evidence indicates the existence a complex pathophysiological relationship between cardiovascular diseases and cancer. Mitochondria are crucial organelles whose optimal activity is determined by quality control systems, which regulate critical cellular events, ranging from intermediary metabolism calcium signaling to mitochondrial dynamics, cell death mitophagy. Emerging data indicate that impaired drives myocardial dysfunction occurring in several heart diseases, including cardiac hypertrophy, infarction, ischaemia/reperfusion damage metabolic cardiomyopathies. On other hand, diverse human cancers also dysregulate promote their initiation progression, suggesting modulating homeostasis may represent promising therapeutic strategy both cardiology oncology. In this review, first we briefly introduce physiological mechanisms underlying system, then summarize current understanding about impact dysregulated functions We discuss key increased risk complications secondary main anticancer strategies, highlighting potential strategies aimed at alleviating impairment-related tumorigenesis. It hoped summary can provide novel insights into precision medicine approaches reduce cancer morbidities mortalities.

Language: Английский

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Deciphering the mechanisms, biochemistry, physiology, and social habits in the process of aging

Archives of Gerontology and Geriatrics Plus, Journal Year: 2023, Volume and Issue: 1(1), P. 100003 - 100003

Published: Dec. 25, 2023

Aging is a complex journey shaped by interactions among mechanisms, biochemistry, physiology, and social habits. This review explores aging's core facets uncovering the mechanisms driving cellular senescence, oxidative stress, telomere shortening, mitochondrial dysfunction. The also delves into biochemistry physiology of aging, shedding light on hormonal shifts, genetic influences, immune system modifications that contribute to aging process. It navigates terrain habits linked considering profound impact dietary choices, physical activity, engagement, stress management. These elements intricately intertwine, emphasizing holistic nature aging. interplay between underscores need for comprehensive understanding transcends single disciplines. Deciphering these factors significance personalized approaches healthy Tailoring interventions individual genetics, lifestyles, health needs emerges as critical strategy optimizing well-being in later life. In conclusion, this illuminates multifaceted urging embrace complexity interdependence. By fostering holistic, approach, individuals can navigate with grace, vitality, resilience.

Language: Английский

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Differential Expression of Nuclear-Encoded Mitochondrial Protein Genes of ATP Synthase Across Different Tissues of Female Buffalo

Molecular Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 2, 2024

Language: Английский

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Variants in Human ATP Synthase Mitochondrial Genes: Biochemical Dysfunctions, Associated Diseases, and Therapies

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2239 - 2239

Published: Feb. 13, 2024

Mitochondrial ATP synthase (Complex V) catalyzes the last step of oxidative phosphorylation and provides most energy (ATP) required by human cells. The mitochondrial genes MT-ATP6 MT-ATP8 encode two subunits multi-subunit Complex V. Since discovery first variant in year 1990 as cause Neuropathy, Ataxia, Retinitis Pigmentosa (NARP) syndrome, a large continuously increasing number inborn variants have been identified pathogenic. Variants these correlate with various clinical phenotypes, which include several neurodegenerative multisystemic disorders. In present review, we report pathogenic highlight molecular mechanisms underlying deficiency that promote biochemical dysfunctions. We discuss possible structural changes induced common found patients considering recent cryo-electron microscopy structure synthase. Finally, provide state-of-the-art all therapeutic proposals reported literature, including drug interventions targeting dysfunctions, allotopic gene expression- nuclease-based strategies, their potential translation into trials.

Language: Английский

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Functional and Morphological Differences of Muscle Mitochondria in Chronic Fatigue Syndrome and Post-COVID Syndrome

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1675 - 1675

Published: Jan. 30, 2024

Patients suffering from chronic fatigue syndrome (CFS) or post-COVID (PCS) exhibit a reduced physiological performance capability. Impaired mitochondrial function and morphology may play pivotal role. Thus, we aimed to measure the muscle oxidative phosphorylation (OXPHOS) capacity assess in CFS PCS patients comparison healthy controls (HCs). Mitochondrial OXPHOS was measured permeabilized fibers using high-resolution respirometry. (subsarcolemmal/intermyofibrillar form/cristae/diameter/circumference/area) content (number proportion/cell) were assessed via electron microscopy. Analyses included differences between HC, CFS, PCS, whereas comparisons morphology/content made for vs. PCS. of complex I, which compared HC. While subsarcolemmal area, volume/cell, diameter, perimeter higher no difference observed these variables intermyofibrillar mitochondria. Both cristae integrity CFS. increased impaired function, but progressed pathological morphological changes suggest structural due prolonged inactivity unknown molecular causes. Instead, significantly lower I activity suggests probably direct virus-induced alterations.

Language: Английский

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Sex differences in frailty among older adults

Experimental Gerontology, Journal Year: 2023, Volume and Issue: 184, P. 112333 - 112333

Published: Dec. 1, 2023

By definition, aging is a natural, gradual and continuous process. On the other hand, frailty reflects increase in vulnerability to stressors shortens time without disease (health span) while longevity refers length of life (lifespan). The average expectancy has significantly increased during last few decades. A longer lifespan been accompanied by an decreased independence older adults, with major differences existing between men women. For example, women tend live than but also experience higher rates disability. Sex prevent optimization lifestyle interventions therapies effectively frailty. are rooted complex interplay uncontrollable (genetic, epigenetic, physiological), controllable factors (psychosocial factors). Thus, understanding underlying causes sex essential for developing personalized promote healthy improve quality In this review, we have discussed key contributors knowledge gaps related

Language: Английский

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