Replicative Senescence in Mesenchymal Stem Cells: An In Vitro Study on Mitochondrial Dynamics and Metabolic Alterations DOI Creative Commons

Beatrice Casorati,

Isabella Zafferri, Sara Castiglioni

и другие.

Antioxidants, Год журнала: 2025, Номер 14(4), С. 446 - 446

Опубликована: Апрель 8, 2025

Mesenchymal stem cells (MSCs) are multipotent progenitors capable of self-renewal and differentiation into various cell lineages, making them essential for tissue repair regenerative medicine. However, their potential is constrained by replicative senescence, an irreversible growth arrest that occurs after a finite number divisions. In this study, we serially passaged human bone marrow-derived MSCs (bMSCs) compared young, pre-senescent, senescent cells. The onset senescence was accompanied progressive alterations in mitochondrial dynamics, leading to decline membrane potential, increased reactive oxygen species (ROS) production, alongside diminished cellular antioxidant capacity. These defects play role metabolic reprogramming bMSCs. Our findings underscore the intricate interplay between ROS, dysfunction, offering valuable insights guide development therapeutic strategies preserving MSC functionality aging MSC-based therapies.

Язык: Английский

Targeting Mitochondrial Dysfunction and Reactive Oxygen Species for Neurodegenerative Disease Treatment DOI Open Access
Eui-Hwan Choi, Mi-Hye Kim, Sun-Ji Park

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(14), С. 7952 - 7952

Опубликована: Июль 21, 2024

Alzheimer's disease (AD) and Parkinson's (PD) are the most common neurodegenerative diseases, they affect millions of people worldwide, particularly older individuals. Therefore, there is a clear need to develop novel drug targets for treatment age-related diseases. Emerging evidence suggests that mitochondrial dysfunction reactive oxygen species (ROS) generation play central roles in onset progression Mitochondria key regulators respiratory function, cellular energy adenosine triphosphate production, maintenance redox homeostasis, which essential cell survival. Mitochondrial morphology function tightly regulated by maintaining balance among fission, fusion, biogenesis, mitophagy. In this review, we provide an overview main functions mitochondria, with focus on recent progress highlighting critical role ROS-induced oxidative stress, dysregulated dynamics, apoptosis, mitochondria-associated inflammation, impaired pathogenesis such as AD PD. We also discuss potential fusion biogenesis enhancers, fission inhibitors, mitochondria-targeted antioxidants drugs these

Язык: Английский

Процитировано

18
Ferroptosis triggers mitochondrial fragmentation via Drp1 activation DOI Creative Commons
Lohans Pedrera,

Laura Prieto Clemente,

Alina Dahlhaus

и другие.

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 25, 2025

Abstract Constitutive mitochondrial dynamics ensure quality control and metabolic fitness of cells, their dysregulation has been implicated in various human diseases. The large GTPase Dynamin-related protein 1 (Drp1) is intimately involved mediating constitutive fission cell death pathways. During ferroptosis, a recently identified type regulated necrosis driven by excessive lipid peroxidation, fragmentation observed. Yet, how this whether it ferroptotic remained unexplored. Here, we provide evidence that Drp1 activated upon experimental induction ferroptosis promotes execution fragmentation. Using time-lapse microscopy, found induced loss membrane potential, but not outer permeabilization. Importantly, accelerated kinetics. Notably, function was mediated the regulation dynamics, as overexpression Mitofusin 2 phenocopied effect deficiency delaying Mechanistically, phosphorylated after translocates to mitochondria. Further activation at mitochondria through phosphatase PGAM5 promoted death. Remarkably, depletion delayed plasma peroxidation. These data for functional role acceleration death, with important implications targeting diseases associated ferroptosis.

Язык: Английский

Процитировано

3
Mitochondrial dysfunction at the crossroad of cardiovascular diseases and cancer DOI Creative Commons
Carmine Rocca, Teresa Soda, Ernestina Marianna De Francesco

и другие.

Journal of Translational Medicine, Год журнала: 2023, Номер 21(1)

Опубликована: Сен. 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.

Язык: Английский

Процитировано

33
Targeting mitochondrial shape: at the heart of cardioprotection DOI Creative Commons
Sauri Hernández‐Reséndiz, Aishwarya Prakash, Sze Jie Loo

и другие.

Basic Research in Cardiology, Год журнала: 2023, Номер 118(1)

Опубликована: Ноя. 13, 2023

There remains an unmet need to identify novel therapeutic strategies capable of protecting the myocardium against detrimental effects acute ischemia-reperfusion injury (IRI), reduce myocardial infarct (MI) size and prevent onset heart failure (HF) following infarction (AMI). In this regard, perturbations in mitochondrial morphology with imbalance fusion fission can disrupt metabolism, calcium homeostasis, reactive oxygen species production, factors which are all known be critical determinants cardiomyocyte death IRI. As such, approaches directed at preserving functionality mitochondria may provide important strategy for cardioprotection. article, we overview alterations occur response IRI, highlight emerging targeting shape preserve function have future potential improve health outcomes patients presenting AMI.

Язык: Английский

Процитировано

25
Altered Mitochondrial Function in MASLD: Key Features and Promising Therapeutic Approaches DOI Creative Commons
Tatjana Radosavljević,

Milica Branković,

Janko Samardžić

и другие.

Antioxidants, Год журнала: 2024, Номер 13(8), С. 906 - 906

Опубликована: Июль 26, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty (NAFLD), encompasses a range of conditions from steatosis to steatohepatitis (NASH). Its prevalence, especially among patients with metabolic syndrome, highlights its growing global impact. The pathogenesis MASLD involves dysregulation, inflammation, oxidative stress, genetic factors and, notably, mitochondrial dysfunction. Recent studies underscore the critical role dysfunction in MASLD's progression. Therapeutically, enhancing function has gained interest, along lifestyle changes and pharmacological interventions targeting processes. FDA's approval resmetirom for metabolic-associated (MASH) fibrosis marks significant step. While represents progress, further research is essential understand MASLD-related fully. Innovative strategies like gene editing small-molecule modulators, alongside interventions, can potentially improve treatment. Drug repurposing new targets will advance therapy, addressing increasing burden. Therefore, this review aims provide better understanding identify more effective preventive treatment strategies.

Язык: Английский

Процитировано

12
BDNF-TrkB Signaling in Mitochondria: Implications for Neurodegenerative Diseases DOI
Smijin Soman, Maryann Swain, Ruben K. Dagda

и другие.

Molecular Neurobiology, Год журнала: 2024, Номер unknown

Опубликована: Июль 19, 2024

Язык: Английский

Процитировано

11
Mitochondrial Dysfunction in Endothelial Progenitor Cells: Unraveling Insights from Vascular Endothelial Cells DOI Creative Commons
Azra Kulovic‐Sissawo, Carolina Tocantins, Mariana S. Diniz

и другие.

Biology, Год журнала: 2024, Номер 13(2), С. 70 - 70

Опубликована: Янв. 23, 2024

Endothelial dysfunction is associated with several lifestyle-related diseases, including cardiovascular and neurodegenerative it contributes significantly to the global health burden. Recent research indicates a link between risk factors (CVRFs), excessive production of reactive oxygen species (ROS), mitochondrial impairment, endothelial dysfunction. Circulating progenitor cells (EPCs) are recruited into vessel wall maintain appropriate function, repair, angiogenesis. After attachment, EPCs differentiate mature (ECs). Like ECs, also susceptible CVRFs, metabolic chronic inflammation. Therefore, may have long-term effects on function ECs which differentiate, particularly in presence damage. However, CVRFs impaired has hardly been investigated. In this review, we aim consolidate existing knowledge development vascular endothelium, place context recent studies investigating consequences EPCs, discuss role Thus, gain comprehensive understanding mechanisms involved EPC deterioration relation address potential therapeutic interventions targeting promote function.

Язык: Английский

Процитировано

9
Mitochondrial quality control: Biochemical mechanism of cardiovascular disease DOI Creative Commons

Francesca Inferrera,

Ylenia Marino,

Tiziana Genovese

и другие.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Год журнала: 2025, Номер 1872(3), С. 119906 - 119906

Опубликована: Янв. 19, 2025

Язык: Английский

Процитировано

1
Overview of neuroimaging in primary mitochondrial disorders DOI
Sedat Giray Kandemirli, Khalid Al‐Dasuqi, Bülent Aslan

и другие.

Pediatric Radiology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 12, 2025

Язык: Английский

Процитировано

1
GLIS1 alleviates cell senescence and renal fibrosis through PGC1-α mediated mitochondrial quality control in kidney aging DOI Creative Commons
Xu Li, Jiao Wang, Hongyuan Yu

и другие.

Free Radical Biology and Medicine, Год журнала: 2023, Номер 209, С. 171 - 184

Опубликована: Окт. 16, 2023

Mitochondrial dysfunction is implied as a crucial factor in age-related chronic kidney disease. It confirmed that Gli-like transcription 1 (GLIS1) involved renal fibrosis, however, the correlation between mitochondrial disturbances and GLIS1-driven aging are not clearly clarified. Thus, we investigated regulatory mechanism of GLIS1 homeostasis quality control both vivo vitro. The lower expression was identified natural accelerated aged models, accompanied by dysfunctions control, including enhanced fission, reduced biogenesis mitophagy, whereas, could maintain stability interacting with peroxisome proliferator-activated receptor γ coactivator-1α (PGC1-α). Additionally, over-expressed inhibited extracellular matrix accumulation alleviated fibrosis while siGLIS1 PGC1-α transcription, well affecting its mitochondria-protective functions. Collectively, demonstrated mediated through targeting aging, which might be promising therapeutic target for attenuating cell senescence fibrosis.

Язык: Английский

Процитировано

16