Mitochondrial Dysfunction in Endothelial Cells: A Key Driver of Organ Disorders and Aging

Antioxidants, Journal Year: 2025, Volume and Issue: 14(4), P. 372 - 372

Published: March 21, 2025

Mitochondria are of great importance in cell biology since they major sites adenosine triphosphate (ATP) production and widely involved different cellular pathways the response to stress. During ATP production, reactive oxygen species (ROS) can be produced. While a small amount ROS may important for regulation physiological processes, at elevated levels turn into harmful agents leading damage. From pathological perspective, it could particularly interesting focus on mitochondrial function endothelial cells development aging onset diseases, including renal, cardio-metabolic, liver neurodegenerative ones. However, date, there no surveys which address above issues. To fill this gap, valuable collect recent findings about role mitochondria function, not only increase knowledge but also clinical applications. Here, we overview most issues view characterizing as an innovative potential target prevention aging, well treatment conditions.

Language: Английский

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Metal Complexes in Target-Specific Anticancer Therapy: Recent Trends and Challenges

Journal of Chemistry, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 19

Published: May 17, 2022

Cancer is characterized by abnormal cell differentiation in or on the part of body. The most commonly used chemotherapeutic drugs are developed to target rapidly dividing cells, such as cancer but they also damage healthy epithelial cells. This has serious consequences for normal cells and become responsible development various disorders. Several strategies delivering cytotoxic cancerous sites that limit systemic toxicity other adverse effects have recently been evolved. Among them, biomolecule-conjugated metal complexes-based targeting shown tremendous advantages therapy. review focuses several chemoselective biomolecules-bound complexes prospective therapy-targeted agents. In this review, we presented details extra- intracellular mechanisms We addressed current clinical issues recent therapeutic targeted therapy may pave a way future direction

Language: Английский

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Treatment and prevention of pathological mitochondrial dysfunction in retinal degeneration and in photoreceptor injury

Biochemical Pharmacology, Journal Year: 2022, Volume and Issue: 203, P. 115168 - 115168

Published: July 12, 2022

Pathological deterioration of mitochondrial function is increasingly linked with multiple degenerative illnesses as a mediator wide range neurologic and age-related chronic diseases, including those genetic origin. Several these diseases are rare, typically defined in the United States an illness affecting fewer than 200,000 people U.S. population, or about one 1600 individuals. Vision impairment due to dysfunction eye prominent feature evident numerous primary common pathophysiology many familiar ophthalmic disorders, macular degeneration, diabetic retinopathy, glaucoma retinopathy prematurity — collection syndromes, disorders significant unmet medical needs. Focusing on metabolic pathway mechanisms, possible roles cuproptosis ferroptosis retinal dysfunction, we shed light potential α-lipoyl-L-carnitine treating diseases. α-Lipoyl-L-carnitine bioavailable mitochondria-targeting lipoic acid prodrug that has shown protecting against degeneration photoreceptor cell loss indications.

Language: Английский

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Downregulation of Aging-Associated Gene SUCLG1 Marks the Aggressiveness of Liver Disease

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 339 - 339

Published: Jan. 21, 2025

Introduction: The most common liver disease is nonalcoholic fatty disease, characterized by an intrahepatic accumulation of lipids that often accompanies obesity. Fatty can evolve, in the presence oxidative stress and inflammation, into disabling deadly diseases such as cirrhosis, hepatocellular carcinoma (HCC), cholangiocarcinoma (CC). Old age seems to favor HCC CC, agreement with inflammaging theory, according which aging accrues inflammation. Cancer, general, age-related incidence mortality for types cancer increase age. However, how molecular drivers tumors differ or are mutated more frequently among patients different ages remains scarcely investigated. A recent integrative analysis age-associated multi-omic landscape across cancers healthy tissues demonstrated gene expression changes linked numerous biological processes. CC have lowest five-year survival estimates due their aggressive progression. Materials methods: In this study, we extracted top candidates from above-mentioned pan-analyses (i.e., B2M, C1qA, SUCLG1) tested qPCR correlation progression 48 tissue samples covering stages (fatty liver, hepatitis, CC) normal tissues. Results: Here, report a significant downregulation SUCLG1 during toward also associates poor patient survival. Conclusion: SUCGL1, mitochondrial enzyme catalyzes conversion succinyl CoA succinate, might be therapeutically targeted development low rates.

Language: Английский

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Therapeutic Approach to Epilepsy in Patients with Mitochondrial Diseases

Yonsei Medical Journal, Journal Year: 2025, Volume and Issue: 66

Published: Jan. 1, 2025

Mitochondrial diseases (MDs) are genetic disorders with diverse phenotypes that affect high-energy-demand organs, notably the central nervous system and muscles. Epilepsy is a common comorbidity, affecting 40%-60% of patients MDs significantly reducing their quality life. This review discusses different treatment modalities for epilepsy in MDs. Advances sequencing have identified specific mutations mitochondrial nuclear DNA, enabling more precise diagnoses tailored therapeutic strategies. Anti-seizure medications dietary interventions, such as ketogenic diets variants, been effective seizures improving function. Emerging treatments include gene therapy, transplantation, antioxidants EPI-743, which protect integrity improve neurological Additionally, therapies promote biogenesis, bezafibrate epicatechin, being explored potential to enhance proliferation energy production. Gene therapy aims correct defects underlying Techniques like replacement using viral vectors deliver functional genes shown promise preclinical studies. an emerging experimental technique, involves transferring healthy mitochondria into cells dysfunctional mitochondria. technique has demonstrated restore function metabolism models. Patient-derived induced pluripotent stem can model dysfunctions vitro, allowing testing various individual biochemical profiles. The future medicine promising, development targeted personalized strategies offering hope improved management prognosis epilepsy.

Language: Английский

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Deoxynucleoside supplementation ameliorates the disease associated phenotypes in a zebrafish model of RRM2B mtDNA depletion syndrome

Human Molecular Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

Abstract Mitochondrial DNA (mtDNA) depletion syndromes (MDDS) are rare, clinically heterogeneous mitochondrial disorders resulting from nuclear variants in genes of the replication or maintenance machinery. Supplementation with pyrimidine deoxynucleosides have been beneficial patients and mice TK2-related MDDS, however, it has not systematically explored other forms MDDS. To investigate effect deoxynucleoside supplementation mitigating disease due to pathogenic RRM2B variants, we generated a novel zebrafish knock-out model this studied different combinations deoxynucleosides. Zebrafish larvae carrying homozygous nonsense mutation rrm2b present impaired movement, reduced mtDNA copy number elevated lactate. combination was performed, increased numbers when supplemented two purine (dGuo dAdo), while had no even further compromised zebrafish. In parallel number, detected improved movement reduction lactate rrm2b−/− fish, confirming on whole organism. This treatment did result any deleterious wild type heterozygous fish. Our data suggest that may be should investigated RRM2B-related disease, adding growing evidence is valid therapeutic approach which can trialled for treating wider range genetic

Language: Английский

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Gene Therapeutic Approaches for the Treatment of Mitochondrial Dysfunction in Parkinson’s Disease

Genes, Journal Year: 2021, Volume and Issue: 12(11), P. 1840 - 1840

Published: Nov. 22, 2021

Mitochondrial dysfunction has been identified as a pathophysiological hallmark of disease onset and progression in patients with Parkinsonian disorders. Besides the overall emergence gene therapies treating these patients, this highly relevant molecular concept not yet defined target for therapeutic approaches.This narrative review will discuss experimental evidence suggesting mitochondrial viable treatment monogenic idiopathic Parkinson's disease. In addition, we focus on general strategies crucial challenges which need to be overcome.Our current understanding biology parkinsonian disorders opens up avenue Insights can obtained from primary diseases. However, substantial knowledge gaps unique mitochondria-targeted addressed provide innovative treatments future.Mitochondria-targeted are potential strategy improve an important mechanism further studies needed address design therapies.

Language: Английский

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Decoding the mitochondria without a code: mechanistic insights into mitochondrial DNA depletion syndromes

Journal of Biosciences, Journal Year: 2024, Volume and Issue: 49(1)

Published: Feb. 19, 2024

Language: Английский

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Understanding the interplay between dNTP metabolism and genome stability in cancer

Disease Models & Mechanisms, Journal Year: 2024, Volume and Issue: 17(8)

Published: Aug. 1, 2024

ABSTRACT The size and composition of the intracellular DNA precursor pool is integral to maintenance genome stability, this relationship fundamental our understanding cancer. Key aspects carcinogenesis, including elevated mutation rates induction certain types damage in cancer cells, can be linked disturbances deoxynucleoside triphosphate (dNTP) pools. Furthermore, approaches treat heavily exploit metabolic interplay between dNTP pool, with a long-standing example being use antimetabolite-based therapies, strategy continues show promise development new targeted therapies. In Review, we compile current knowledge on both causes consequences perturbations together their impact stability. We outline several outstanding questions remaining field, such as role catabolism stability expansion. Importantly, detail how mechanistic these processes utilised aim providing better informed treatment options patients

Language: Английский

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Mice lacking the mitochondrial exonuclease MGME1 develop inflammatory kidney disease with glomerular dysfunction

PLoS Genetics, Journal Year: 2022, Volume and Issue: 18(5), P. e1010190 - e1010190

Published: May 9, 2022

Mitochondrial DNA (mtDNA) maintenance disorders are caused by mutations in ubiquitously expressed nuclear genes and lead to syndromes with variable disease severity tissue-specific phenotypes. Loss of function the gene encoding mitochondrial genome exonuclease 1 (MGME1) result deletions depletion mtDNA leading adult-onset multisystem humans. To better understand vivo MGME1 associated pathophysiology, we characterized a Mgme1 mouse knockout model extensive phenotyping ageing animals. We show that loss leads de novo formation linear deleted fragments constantly made degraded. These findings contradict previous proposal is essential for degradation instead support where has critical role completion replication. report mice develop dramatic phenotype as they age display progressive weight loss, cataract retinopathy. Surprisingly, aged animals also kidney inflammation, glomerular changes severe chronic nephropathy, consistent nephrotic syndrome. link faulty synthesis inflammatory thus defective replication can trigger an immune response causes age-associated pathology kidney.

Language: Английский

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