Mitochondrial dysfunction: mechanisms and advances in therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 15, 2024

Abstract Mitochondria, with their intricate networks of functions and information processing, are pivotal in both health regulation disease progression. Particularly, mitochondrial dysfunctions identified many common pathologies, including cardiovascular diseases, neurodegeneration, metabolic syndrome, cancer. However, the multifaceted nature elusive phenotypic threshold dysfunction complicate our understanding contributions to diseases. Nonetheless, these complexities do not prevent mitochondria from being among most important therapeutic targets. In recent years, strategies targeting have continuously emerged transitioned clinical trials. Advanced intervention such as using healthy replenish or replace damaged mitochondria, has shown promise preclinical trials various Mitochondrial components, mtDNA, mitochondria-located microRNA, associated proteins can be potential agents augment function immunometabolic diseases tissue injuries. Here, we review current knowledge pathophysiology concrete examples We also summarize treat perspective dietary supplements targeted therapies, well translational situation related pharmacology agents. Finally, this discusses innovations applications transplantation an advanced promising treatment.

Language: Английский

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The Metabolic Syndrome, a Human Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2251 - 2251

Published: Feb. 13, 2024

This review focuses on the question of metabolic syndrome (MS) being a complex, but essentially monophyletic, galaxy associated diseases/disorders, or just related rather independent pathologies. The human nature MS (its exceptionality in Nature and its close interdependence with action evolution) is presented discussed. text also describes components, special emphasis description their interrelations (including syndromic development recruitment), as well consequences upon energy handling partition. main theories MS’s origin are relation to hepatic steatosis, type 2 diabetes, obesity, encompass most components described so far. differential effects sex biological considered under light social needs evolution, which directly epidemiology, severity, relations senescence. triggering maintenance factors discussed, especial inflammation, complex process affecting different levels organization critical element for development. Inflammation operation connective tissue adipose organ) widely studied acknowledged influence diet. role diet composition, including transcendence anaplerotic Krebs cycle from dietary amino acid supply (and timing), developed context testosterone β-estradiol control insulin-glycaemia core system carbohydrate-triacylglycerol handling. high probability acting unique (essentially monophyletic) presented, together additional perspectives/considerations treatment this ‘very’ disease.

Language: Английский

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Protein cargo in extracellular vesicles as the key mediator in the progression of cancer

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 10, 2024

Abstract Exosomes are small vesicles of endosomal origin that released by almost all cell types, even those pathologically altered. widely participate in cell-to-cell communication via transferring cargo, including nucleic acids, proteins, and other metabolites, into recipient cells. Tumour-derived exosomes (TDEs) many important molecular pathways affect various hallmarks cancer, fibroblasts activation, modification the tumour microenvironment (TME), modulation immune responses, angiogenesis promotion, setting pre-metastatic niche, enhancing metastatic potential, affecting therapy sensitivity resistance. The unique exosome biogenesis, composition, nontoxicity, ability to target specific cells bring up their use as promising drug carriers cancer biomarkers. In this review, we focus on role exosomes, with an emphasis protein key mechanisms promoting progression. We also briefly summarise mechanism its structure, potential a signalling hub both normal pathological conditions.

Language: Английский

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Osteocyte mitochondria inhibit tumor development via STING-dependent antitumor immunity

Science Advances, Journal Year: 2024, Volume and Issue: 10(3)

Published: Jan. 17, 2024

Bone is one of the most common sites tumor metastases. During last step bone metastasis, cancer cells colonize and disrupt matrix, which maintained mainly by osteocytes, abundant in microenvironment. However, role osteocytes metastasis still unclear. Here, we demonstrated that transfer mitochondria to metastatic trigger cGAS/STING-mediated antitumor response. Blocking specifically knocking out mitochondrial Rho GTPase 1 ( Rhot1 ) or mitofusin 2 Mfn2 impaired immunogenicity consequently resulted progression toward matrix. These findings reveal protective against transferring potentially offer a valuable therapeutic strategy for preventing metastasis.

Language: Английский

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Recommendations for mitochondria transfer and transplantation nomenclature and characterization

Nature Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Language: Английский

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Mitohormesis

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(11), P. 1872 - 1886

Published: Nov. 1, 2023

Language: Английский

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MitoTracker: A useful tool in need of better alternatives

European Journal of Cell Biology, Journal Year: 2023, Volume and Issue: 102(4), P. 151371 - 151371

Published: Oct. 31, 2023

The fluorescence viewing of mitochondria is commonly performed by MitoTracker, a lipophilic cationic dye that taken up the mitochondria. In this forum, we highlight several issues may occur with including staining other organelles. Our aim to offer alternative dyes and discuss their advantages disadvantages. We also options for software alternatives MitoTracker expedite future experimental design.

Language: Английский

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Aging of the eye: Lessons from cataracts and age-related macular degeneration

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 99, P. 102407 - 102407

Published: July 6, 2024

Aging is the greatest risk factor for chronic human diseases, including many eye diseases. Geroscience aims to understand effects of aging process on these genetic, molecular, and cellular mechanisms that underlie increased disease over lifetime. Understanding increases general knowledge physiology impacted by processes at various biological extremes. Two major age-related cataract macular degeneration (AMD) are caused dysfunction lens retina, respectively. Lens transparency light refraction mediated fiber cells lacking nuclei other organelles, which provides a unique opportunity study single hallmark, i.e., loss proteostasis, within an environment limited metabolism. In AMD, local photoreceptors/retinal pigmented epithelium/Bruch's membrane/choriocapillaris complex in macula leads photoreceptors eventually central vision, driven nearly all hallmarks shares features with Alzheimer's disease, Parkinson's cardiovascular diabetes. The can function as model studying basic and, vice versa, well-defined be used tools disease.

Language: Английский

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Regulation of proteostasis and innate immunity via mitochondria-nuclear communication

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(3)

Published: Feb. 9, 2024

Mitochondria are perhaps best known as the “powerhouse of cell” for their role in ATP production required numerous cellular activities. have emerged an important signaling organelle. Here, we first focus on pathways mediated by mitochondria-nuclear communication that promote protein homeostasis (proteostasis). We examine mitochondrial unfolded response (UPRmt) C. elegans, which is regulated a transcription factor harboring both mitochondrial- and nuclear-targeting sequence, integrated stress mammals, well regulation chromatin metabolites. In second section, explore mitochondria-to-nuclear innate immunity inflammation. Perhaps related to prokaryotic origin, mitochondria harbor molecules also found viruses bacteria. If these accumulate cytosol, they elicit same immune responses viral or bacterial infection.

Language: Английский

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Exercise-induced extracellular vesicles in reprogramming energy metabolism in cancer

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 6, 2025

Cancer is caused by complex interactions between genetic, environmental, and lifestyle factors, making prevention strategies, including exercise, a promising avenue for intervention. Physical activity associated with reduced cancer incidence progression systemic anti-cancer effects, improved tumor suppression prolonged survival in preclinical models. Exercise impacts the body's nutrient balance stimulates release of several exercise-induced factors into circulation. The mechanisms how exercise modulates energy metabolism microenvironment through effects mediated, part, extracellular vesicles (EVs) are still unknown. By transferring bioactive cargo such as miRNAs, proteins metabolites, EVs may influence cells altering glycolysis oxidative phosphorylation, potentially shifting metabolic plasticity - hallmark cancer. This short review explores roles mediators to reprogram cellular exchanging information inside microenvironment, influencing immune cells, fibroblast distant cells. Considering this knowledge, further functional studies production pathways could inform more specific interventions enhance therapy improve patient outcomes.

Language: Английский

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