Impaired Mitochondrial Network Morphology and ROS production in Fibroblasts from Parkinson’s Disease Patients DOI Open Access
Kristina A. Kritskaya, Evgeniya I. Fedotova, Alexey V. Berezhnov

и другие.

Опубликована: Дек. 13, 2023

The mitochondrial network (MN) is a dynamic structure undergoing constant remodeling in the cell. It assumed that violation of MN may be associated with various pathologies, including Parkinson’s disease (PD). Using automatic image analysis and super-resolution microscopy, we have assessed parameters fibroblasts from patients established hereditary PD mutations (associated PINK1, LLRK2, α-synuclein, PINK1 Parkin simultaneously proteins) under normal conditions after hydrogen peroxide-induced stress. Fibroblasts Pink1/Parkin mutation are most different morphology obtained conditionally healthy donors: larger, contains longer mitochondria accumulated individual mitochondria. In addition to MN, evaluated other cellular parameters, such as: cytosolic ROS production membrane potential. has been shown genes encoding α-synuclein Pink/Parkin tends hyperpolarization overproduction, while was higher only mutation.

Язык: Английский

Mitochondrial diseases: from molecular mechanisms to therapeutic advances DOI Creative Commons
Hu Wen,

Hui Deng,

Bingyan Li

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Янв. 9, 2025

Abstract Mitochondria are essential for cellular function and viability, serving as central hubs of metabolism signaling. They possess various metabolic quality control mechanisms crucial maintaining normal activities. Mitochondrial genetic disorders can arise from a wide range mutations in either mitochondrial or nuclear DNA, which encode proteins other contents. These defects lead to breakdown metabolism, such the collapse oxidative phosphorylation, one mitochondria’s most critical functions. diseases, common group disorders, characterized by significant phenotypic heterogeneity. Clinical symptoms manifest systems organs throughout body, with differing degrees forms severity. The complexity relationship between mitochondria diseases results an inadequate understanding genotype-phenotype correlation these historically making diagnosis treatment challenging often leading unsatisfactory clinical outcomes. However, recent advancements research technology have significantly improved our management conditions. translations mitochondria-related therapies actively progressing. This review focuses on physiological mitochondria, pathogenesis potential diagnostic therapeutic applications. Additionally, this discusses future perspectives diseases.

Язык: Английский

Процитировано

2

Multifunctional scaffolds for bone repair following age-related biological decline: Promising prospects for smart biomaterial-driven technologies DOI
Jonathan Schwartzman,

Max McCall,

Yasmine Ghattas

и другие.

Biomaterials, Год журнала: 2024, Номер 311, С. 122683 - 122683

Опубликована: Июнь 28, 2024

Язык: Английский

Процитировано

9

Antioxidants and Mechanistic Insights for Managing Dry Age-Related Macular Degeneration DOI Creative Commons
Deepak Basyal, Sooyeun Lee, Hye Jin Kim

и другие.

Antioxidants, Год журнала: 2024, Номер 13(5), С. 568 - 568

Опубликована: Май 4, 2024

Age-related macular degeneration (AMD) severely affects central vision due to progressive and its staggering prevalence is rising globally, especially in the elderly population above 55 years. Increased oxidative stress with aging considered an important contributor AMD pathogenesis despite multifaceted risk factors including genetic predisposition environmental agents. Wet can be managed routine intra-vitreal injection of angiogenesis inhibitors, but no satisfactory medicine has been approved for successful management dry form. The toxic carbonyls photo-oxidative degradation accumulated bisretinoids within lysosomes initiate a series events protein adduct formation, impaired autophagy flux, complement activation, chronic inflammation, which implicated AMD. Therapy based on antioxidants extensively studied promising effect reducing impact stress. This paper reviews pathogenesis, delineates effectiveness dietary nutrition supplements clinical studies, explores pre-clinical studies antioxidant molecules, extracts, formulations their mechanistic insights.

Язык: Английский

Процитировано

7

Sphingolipid long chain bases as mediators of cell death in olive fruit abscission DOI
Beatriz Briegas,

Maria C. Camarero,

Jorge Corbacho

и другие.

Physiologia Plantarum, Год журнала: 2025, Номер 177(1)

Опубликована: Янв. 1, 2025

Abstract Plant sphingolipids are lipophilic membrane components essential for different cellular functions but they also act as signaling molecules in various aspects of plant development. However, the interaction between and abscission remains largely uncharacterized. Here, possible role regulating fruit was examined zone (AZ) olive fruit. To this end, sphingolipid levels were manipulated through application exogenous long‐chain bases (LCBs) or biosynthesis inhibitors, their effects on well LCB/gene expression, hormones, reactive oxygen species (ROS) cell death AZ Our data indicated that sphinganine (d18:0) induced abscission, whereas sphingosine (d18:1) phytosphingosine (t18:0) phosphorylated derivatives did not have an effect abscission. Moreover, inhibition LCB kinase ceramide synthase, which increases AZ, reduced break strength. This induction is associated with elevated ROS enriched salicylic acid (SA) jasmonic (JA). Along same line, programmed (PCD) particularly evident distal side AZ. These suggest endogenous d18:0 plays a key molecule functioning upstream SA/JA pathway mediating PCD spatially regulated during Overall, findings reported here provide insight into complex connection LCBs, uncovering process.

Язык: Английский

Процитировано

0

Platycodi radix aqueous extract salvages doxorubicin‐induced senescence by mitochondrial reactive oxygen species reduction in umbilical cord matrix stem cells DOI

Pei‐Ying Lee,

Maria Angelina Sitorus,

Chia‐Hua Kuo

и другие.

Environmental Toxicology, Год журнала: 2024, Номер 39(7), С. 3872 - 3882

Опубликована: Апрель 1, 2024

Abstract Platycodi radix is a widely used herbal medicine that contains numerous phytochemicals beneficial to health. The health and biological benefits of P. have been found across various diseases. utilization umbilical cord stromal stem cells, derived from Wharton's jelly the human cord, has emerged as promising approach for treating degenerative Nevertheless, growing evidence indicates function cells declines with age, thereby limiting their regenerative capacity. primary objective in this study investigate effects senescent cells. We conducted experiments showcase diminished levels Lamin B1 Sox‐2, along an elevation p21, which serve indicative markers Our findings revealed loss coupled increase subjected low‐dose (0.1 μM) doxorubicin (Dox) stimulation. However, restored Dox‐damage reversed conditions when exposed Dox‐induced reactive oxygen species (ROS) mitochondrial membrane potential are significantly changed. In Dox‐challenged aged reduced senescence, increased longevity, prevented dysfunction ROS protected against senescence‐associated apoptosis. This suggests might be therapeutic rescue agent aging effect Inhibition cell death, aging‐associated provides additional insights into underlying molecular mechanisms.

Язык: Английский

Процитировано

3

Impaired Mitochondrial Network Morphology and Reactive Oxygen Species Production in Fibroblasts from Parkinson’s Disease Patients DOI Creative Commons
Kristina A. Kritskaya, Evgeniya I. Fedotova, Alexey V. Berezhnov

и другие.

Biomedicines, Год журнала: 2024, Номер 12(2), С. 282 - 282

Опубликована: Янв. 25, 2024

The mitochondrial network (MN) is a dynamic structure undergoing constant remodeling in the cell. It assumed that perturbations to MN may be associated with various pathologies, including Parkinson's disease (PD). Using automatic image analysis and super-resolution microscopy, we have assessed parameters fibroblasts from patients established hereditary PD mutations (associated PINK1, LRRK2, α-synuclein, as well PINK1 Parkin proteins simultaneously) under normal conditions after hydrogen peroxide-induced stress. Fibroblasts Pink1/Parkin mutation are most different morphology obtained conditionally healthy donors: larger, it contains longer mitochondria accumulated individual mitochondria. In addition MN, evaluated other cellular parameters, such cytosolic ROS production membrane potential. has been shown of genes encoding Pink/Parkin tend towards hyperpolarization overproduction, while was higher only α-synuclein mutations.

Язык: Английский

Процитировано

2

Is localized chemiosmosis necessary in mitochondria? Is Lee's TELP protonic capacitor hypothesis a reasonable model? DOI Creative Commons
Todd P. Silverstein

Mitochondrial Communications, Год журнала: 2024, Номер 2, С. 48 - 57

Опубликована: Янв. 1, 2024

Recent high-resolution pH measurements in mitochondria show ΔpH across the F1F0 ATP synthase to be quite low, 0.07–0.32. Our meta-analysis of published values transmembrane potential (Δψ) shows it identical vivo and vitro: -159 ± 16 mV. With low ΔpH, thermodynamic efficiency proton-driven synthesis exceeds 100 % for average- low-potential (−123 mV) mitochondria, possibly also high-potential (−180 mitochondria. Efficiencies exceeding may violate second law thermodynamics, suggest a need localized chemiosmosis, i.e., existence membrane surface that bulk phase by at least 0.2 units 1.1 The lack equilibration between protons those is explained two models which we discuss compare: well/barrier model, TELP protonic capacitor model.

Язык: Английский

Процитировано

2

Melamine Exacerbates Neurotoxicity in D-Galactose-Induced Neuronal SH-SY5Y Cells DOI Creative Commons
J Goyal, Preet Jain, Vivek Jain

и другие.

Journal of Aging Research, Год журнала: 2023, Номер 2023, С. 1 - 9

Опубликована: Ноя. 23, 2023

Numerous studies have depicted the role of diet and environmental toxins in aging. Melamine (Mel) is a globally known notorious food adulterant, its toxicity has been shown several organs including brain. However, till now, there are no reports regarding Mel neurotoxicity aging neurons. So, this study examined vitro caused by D-galactose (DG)-induced model neuronal SH-SY5Y cells. In present study, cells were treated with DG separately combination to assess potential using MTT assay neurite length measurement. Further, superoxide dismutase (SOD), catalase (CAT), total antioxidant activities evaluated followed determination intracellular reactive oxygen species (ROS), mitochondrial membrane (MMP), caspase3 (Casp3) activity. The cotreatment showed maximum cell death than or individually untreated control shrinkage ROS production cotreated showing exacerbated Mel. activity SOD, CAT, antioxidants was also found be lowered group (Mel + DG) Mel- DG-treated combined elevated Casp3 more any other group. This first increased neurotoxic an which implicates that consumption elderly may lead incidences neurodegeneration like Alzheimer's disease Parkinson's disease.

Язык: Английский

Процитировано

4

Direct toxicity of cigarette smoke extract on cardiac function mediated by mitochondrial dysfunction in Sprague-Dawley rat ventricular myocytes and human induced pluripotent stem cell-derived cardiomyocytes DOI Creative Commons

Sakiko Matsumura,

Jumpei Yasuda,

Takuya Notomi

и другие.

PLoS ONE, Год журнала: 2024, Номер 19(1), С. e0295737 - e0295737

Опубликована: Янв. 2, 2024

Cigarette smoke has been recognized as a major risk factor for cardiovascular disease. However, its direct effects on rodent and human cardiomyocytes cellular mechanisms are not fully understood. In this study, we examined the of cigarette extract (CSE) contractile functions, intracellular Ca 2+ dynamics, mitochondrial function using cultured or freshly isolated rat ventricular myocytes induced pluripotent stem cell (iPS)-derived cardiomyocytes. cardiomyocytes, CSE (≥0.1%) resulted in time- concentration-dependent cessation spontaneous beating eventually leading to death, which indicates toxicity. addition, 1% reduced myocytes. Similar dysfunction (declined rate contractility) was also observed iPS-derived Regarding increased transient amplitude by greatly increasing systolic levels slightly diastolic levels. accelerated decay transients, triggered spike-shaped transients some cells. These results indicate that causes abnormal dynamics Furthermore, cascade dysfunctions, including reactive oxygen species, opening permeability transition pore, reduction membrane potential, release cytochrome c from mitochondria. suggest CSE-induced myocardial death is caused subsequent dysregulation, would result bioenergetics activation pathways.

Язык: Английский

Процитировано

1

Trending toward gero‐electroceuticals that target membrane potential for reprogramming aging and lifespan DOI Creative Commons
Siamak Tabibzadeh, Olen R. Brown

Aging and Cancer, Год журнала: 2024, Номер 5(1-2), С. 3 - 13

Опубликована: Июнь 1, 2024

Abstract Ion gradients across cell membranes generate voltage potentials that are involved in a wide range of biological processes. According to the membrane hypothesis aging, aging is inextricably linked decrease resting potential ( V mem ). Alterations ion channel activity and fluidity caused by disrupt bioelectric homeostasis, increase intracellular calcium potassium concentrations, induce abnormal mechanistic target rapamycin (MTOR)‐ AMPK‐regulated metabolism energy dissipation, proliferation regeneration. Failure maintain leads senescence or death. There evidence manipulating activities, cryptic memory can be recalled restore lost proliferative regenerative abilities. Reversal prevention senescence, phenotypes, longevity may achieved fine‐tuning mitochondrial polarization. Therefore, there optimism deciphering codes govern functions will lead development new gero‐electroceuticals function prevent tissue loss during aging.

Язык: Английский

Процитировано

1