Pharmacologic Activation of Integrated Stress Response Kinases Inhibits Pathologic Mitochondrial Fragmentation DOI Open Access
Kelsey R. Baron, Samantha Oviedo,

Sophia Krasny

et al.

Published: Sept. 25, 2024

Excessive mitochondrial fragmentation is associated with the pathologic dysfunction implicated in pathogenesis of etiologically-diverse diseases, including many neurodegenerative disorders. The integrated stress response (ISR) – comprising four eIF2α kinases PERK, GCN2, PKR, and HRI a prominent stress-responsive signaling pathway that regulates morphology function to diverse types insult. This suggests pharmacologic, stress-independent activation ISR represents potential strategy mitigate human disease. Here, we show or GCN2 promotes adaptive elongation prevents induced by calcium ionophore ionomycin. Further, these reduces restores basal patient fibroblasts expressing pathogenic D414V variant pro-fusion GTPase MFN2 neurological dysfunctions ataxia, optic atrophy, sensorineural hearing loss. These results identify as prevent disease-relevant chemical genetic insults, further motivating pursuit highly selective kinase-activating compounds therapeutic diseases.

Language: Английский

The roles of dietary polyphenols at crosstalk between type 2 diabetes and Alzheimer's disease in ameliorating oxidative stress and mitochondrial dysfunction via PI3K/Akt signaling pathways DOI

Jingwen Wang,

Jingyang Zhang, Zhi‐Ling Yu

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 99, P. 102416 - 102416

Published: July 13, 2024

Language: Английский

Citations

13
Complex II ambiguities—FADH2 in the electron transfer system DOI Creative Commons
Erich Gnaiger

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 300(1), P. 105470 - 105470

Published: Nov. 22, 2023

The prevailing notion that reduced cofactors NADH and FADH

Language: Английский

Citations

19
Effects of carotenoids on mitochondrial dysfunction DOI Creative Commons
Opeyemi Stella Ademowo, Olubukola T. Oyebode,

Roshita Edward

et al.

Biochemical Society Transactions, Journal Year: 2024, Volume and Issue: 52(1), P. 65 - 74

Published: Feb. 22, 2024

Oxidative stress, an imbalance between pro-oxidant and antioxidant status, favouring the state is a result of increased production reactive oxygen species (ROS) or inadequate protection. ROS are produced through several mechanisms in cells including during mitochondrial oxidative phosphorylation. Increased mitochondrial-derived associated with dysfunction, early event age-related diseases such as Alzheimer's (ADs) metabolic disorders diabetes. AD post-mortem investigations affected brain regions have shown accumulation damage to macromolecules, stress has been considered important contributor disease pathology. An increase which leads levels superoxide, hydrogen peroxide other potentially vicious cycle both causative consequence dysfunction. Mitochondrial dysfunction may be ameliorated by molecules capacities that accumulate mitochondria carotenoids. However, role carotenoids mitigating not fully understood. A better understanding antioxidants function promising lead towards development novel effective treatment strategies for diseases. This review evaluates summarises some latest developments insights into effects on focus properties The mitochondria-protective key therapeutic targeting emerging drug

Language: Английский

Citations

5
Pharmacologic Activation of Integrated Stress Response Kinases Inhibits Pathologic Mitochondrial Fragmentation DOI Open Access
Kelsey R. Baron, Samantha Oviedo,

Sophia Krasny

et al.

Published: Jan. 16, 2025

Excessive mitochondrial fragmentation is associated with the pathologic dysfunction implicated in pathogenesis of etiologically-diverse diseases, including many neurodegenerative disorders. The integrated stress response (ISR) – comprising four eIF2α kinases PERK, GCN2, PKR, and HRI a prominent stress-responsive signaling pathway that regulates morphology function to diverse types insult. This suggests pharmacologic activation ISR represents potential strategy mitigate human disease. Here, we show or GCN2 promotes adaptive elongation prevents induced by calcium ionophore ionomycin. Further, reduces restores basal patient fibroblasts expressing pathogenic D414V variant pro-fusion GTPase MFN2 neurological dysfunctions ataxia, optic atrophy, sensorineural hearing loss. These results identify as prevent disease-relevant chemical genetic insults, further motivating pursuit highly selective kinase-activating compounds therapeutic diseases.

Language: Английский

Citations

0
Transcutaneous electrical acustimulation promotes wound healing in mice by modulating signaling molecules and mitochondria function DOI Creative Commons
Han Rong,

M. Chen,

Peng Wang

et al.

Archives of Dermatological Research, Journal Year: 2025, Volume and Issue: 317(1)

Published: Feb. 8, 2025

Abstract Previous research has identified a variety of factors that contribute to the development and maintenance wounds. Concurrently, electroacupuncture been demonstrated facilitate wound healing. However, effects transcutaneous electrical acustimulation (TEA) on healing, as well its relationship with key such Wnt3a, TGF-β, Akt, c-Myc, VEGF-A, SP1, nitric oxide (NO), mitochondrial function, remain largely unexplored. We hypothesize TEA will activate signaling enhance functions promote repair skin wounds in mice. An vivo experimental study was conducted utilizing mouse models The comprised three groups: treatment group, model control group. Wound areas were measured by calculating product length width each using calipers. Single-cell suspensions prepared excising immediately surrounding tissue. These stained Trypan blue assess cell viability, specific probes measure rate reactive oxygen species (ROS) positivity, reagents quantify NO content. Western blotting (WB) employed evaluate protein levels associated tissue changes, while quantitative polymerase chain reaction (qPCR) used RNA expression levels. Immunofluorescence staining performed visualize content other relevant cellular structures within sections. exhibited anti-inflammatory properties promoted healing blot analysis revealed enhanced proteins SP1 during process. sections indicated upregulated COL1A1, MFN1, GRP75, GRP78, GRP75/ROS, GRP78/ROS, ISCU, UCP1 downregulating FIS1. Additionally, qPCR results IL-10 miRNA205-5p inhibiting MMP9 modulates various molecules, influences chaperone related stress recovery responses, along dynamics metabolism. Graphical abstract

Language: Английский

Citations

0
Pharmacologic activation of integrated stress response kinases inhibits pathologic mitochondrial fragmentation DOI Creative Commons
Kelsey R. Baron, Samantha Oviedo,

Sophia Krasny

et al.

eLife, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 12, 2025

Excessive mitochondrial fragmentation is associated with the pathologic dysfunction implicated in pathogenesis of etiologically diverse diseases, including many neurodegenerative disorders. The integrated stress response (ISR) – comprising four eIF2α kinases PERK, GCN2, PKR, and HRI a prominent stress-responsive signaling pathway that regulates morphology function to types insult. This suggests pharmacologic activation ISR represents potential strategy mitigate human disease. Here, we show or GCN2 promotes adaptive elongation prevents induced by calcium ionophore ionomycin. Further, reduces restores basal patient fibroblasts expressing pathogenic D414V variant pro-fusion GTPase MFN2 neurological dysfunctions, ataxia, optic atrophy, sensorineural hearing loss. These results identify as prevent disease-relevant chemical genetic insults, further motivating pursuit highly selective kinase-activating compounds therapeutic diseases.

Language: Английский

Citations

0
Dihydromyricetin regulates RIPK3-CaMKII to prevent necroptosis in high glucose-stimulated cardiomyocytes DOI Creative Commons
Linlin Sun,

Yujiao Xiao,

Wenqing San

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(7), P. e28921 - e28921

Published: March 29, 2024

Diabetic cardiomyopathy is one common cardiovascular complication without effective treatments. Dihydromyricetin (DHY), a natural dihydroflavonol compound extracted from Ampelopsis grossedentata, possesses versatile pharmacologically important effects. In our current research, we planned to evaluate the impact and probable DHY mechanisms in high glucose (HG)-induced cardiomyocytes. Primary cardiomyocytes were pretreated with different concentrations of (0, 20, 40, 80, 160, 320 μM) for various time 1, 2, 4, 12, 24 h). They then stimulated 48 h 5.5 mmol/L normal (NG) 33.3 (HG). Cell viability, adenosine-triphosphate (ATP) levels, lactate dehydrogenase (LDH) release detected. JC-1 staining was employed measure mitochondrial membrane potential. MitoSOX dihydroethidium (DHE) applied oxidative stress levels. TDT mediated dUTP nick end labeling (TUNEL) used apoptotic Expressions calcium/calmodulin-dependent protein kinase II (CaMKII), phospholamban (PLB), optic atrophy 1 (OPA1), dynamin-related (DRP1), caspase 3, mixed lineage domain like (MLKL), receptor interacting 3 (RIPK3), (RIPK1) detected by immunofluorescence and/or Western blot. improved cell enhanced ATP level, decreased LDH content HG-stimulated cardiomyocytes, suggesting attenuating injury. reduced number TUNEL positive cells, inhibited RIPK3 cleaved-caspase expression, implying alleviated necroptosis diminished monomers, DHE fluorescence intensity as well DRP1 expression but increased aggregates OPA1 indicating that attenuated also CaMKII activity suppressed PLB phosphorylation oxidation HG-induced injury wherein necroptosis, repressed ROS production, oxidation, may serve potential agent prevent treat diabetic cardiomyopathy.

Language: Английский

Citations

4
Ferulic acid restores mitochondrial dynamics and autophagy via AMPK signaling pathway in a palmitate-induced hepatocyte model of metabolic syndrome DOI Creative Commons
Yitong Li,

Weiyang Zhao,

Ali Tahir Sair

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 16, 2024

Mitochondrial dysfunction, characterized by elevated oxidative stress, impaired energy balance, and dysregulated mitochondrial dynamics, is a hallmark of metabolic syndrome (MetS) its comorbidities. Ferulic acid (FA), principal phenolic compound found in whole grains, has demonstrated potential ameliorating stress preserving homeostasis. However, the influence FA on health within context MetS remains unexplored. Moreover, impact autophagy, which essential for maintaining homeostasis integrity, not fully understood. Here, we aimed to study mechanisms action regulating autophagy using palmitate-treated HepG2 hepatocytes as cell model. We that improved restoring redox balance optimizing including biogenesis fusion/fission ratio. Additionally, was shown recover activate AMPK-related signaling. Our results provide new insights into therapeutic mitochondria-targeting agent prevention treatment MetS.

Language: Английский

Citations

4
Protective Effects of Mdivi‐1 on Cognition Disturbance Following Sepsis in Mice via Alleviating Microglia Activation and Polarization DOI Creative Commons
Chen Hong, Li Wang, Xiaowei Zhou

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(1)

Published: Jan. 1, 2025

Neuroinflammation is one of the essential pathogeneses cognitive damage suffering from sepsis-associated encephalopathy (SAE). Lots evidences showed microglia presented mitochondrial fragmentation during SAE. This study investigated protective effects and novel mechanisms inhibiting via division inhibitor 1 (Mdivi-1) on in The SAE model was performed by cecal ligation puncture (CLP), Mdivi-1 administrated intraperitoneal injection. Morris water maze to assess function. Mitochondrial morphology observed electron microscope or MitoTracker staining. qRT-PCR, immunofluorescence staining, western blots were used detect inflammatory factors protein content, respectively. Flow cytometry polarization hippocampal microglia. Bioinformatics analysis verify hypotheses. administration alleviated sepsis-induced fragmentation, activation, polarization, damage. neuroinflammation oxidative stress suppressed NF-κB Keap1/Nrf2/HO-1 pathways following administration; meanwhile, pyroptosis reduced, which associated with enhanced autophagosome formation p62 elevation administration. Inhibition beneficial disturbance, are related alleviating neuroinflammation, stress, pyroptosis.

Language: Английский

Citations

0
Regular exercise alleviates metabolic dysfunction-associated steatohepatitis through rescuing mitochondrial oxidative stress and dysfunction in liver DOI
Baoxuan Lin, Tong Wu, Mohammad Nasb

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0