Newly imported proteins in mitochondria are particularly sensitive to aggregation DOI Creative Commons
Carmela Vazquez‐Calvo, Verena Kohler, Johanna L. Höög

et al.

Acta Physiologica, Journal Year: 2023, Volume and Issue: 238(3)

Published: May 12, 2023

A functional proteome is essential for life and maintained by protein quality control (PQC) systems in the cytosol organelles. Protein aggregation an indicator of a decline PQC linked to aging disease. Mitochondrial critical maintain mitochondrial function thus cellular fitness. How mitochondria handle aggregated proteins not well understood. Here we tested how metabolic status impacts on formation clearance aggregates within yeast assessed which are particularly sensitive denaturation.

Language: Английский

Reactive Oxygen Species Control Osteoblast Apoptosis through SIRT1/PGC-1α/P53Lys382 Signaling, Mediating the Onset of Cd-Induced Osteoporosis DOI

Di Ran,

Dehui Zhou,

Gang Liu

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: unknown

Published: April 6, 2023

The imbalance between osteogenesis and osteoclastogenesis is a feature of bone metabolic disease. Cadmium (Cd) exposure causes human loss osteoporosis (OP) through bioaccumulation the food chain. However, impact Cd on tissues underlying molecular mechanisms are not well-characterized. In current study, we found that concentration in OP patients was higher than normal subjects; meanwhile, nuclear silent information regulator transcription 1 (SIRT1) protein expression level significantly decreased, which new star molecule to treat OP. It further revealed SIRT1 activation markedly reprograms stress-response pathways incline with osteoblast (OB) apoptosis. Suppressing reactive oxygen species (ROS) release N-acetyl-l-cysteine (NAC) abolished Cd-induced reduction protein, deacetylation P53, OB apoptosis, attenuated Conversely, overexpression suppressed ROS release. vivo vitro dampened PGC-1α acetylation P53 at lysine 382, caspase-dependent These results reveal ROS/SIRT1 controls coordinates apoptosis involved onset

Language: Английский

Citations

13
A Mitochondria‐Related Signature in Diffuse Large B‐Cell Lymphoma: Prognosis, Immune and Therapeutic Features DOI Creative Commons
Zhiwei Zhou, Jiabin Lu, Song‐Bin Guo

et al.

Cancer Medicine, Journal Year: 2025, Volume and Issue: 14(2)

Published: Jan. 1, 2025

ABSTRACT Background Distinctive heterogeneity characterizes diffuse large B‐cell lymphoma (DLBCL), one of the most frequent types non‐Hodgkin's lymphoma. Mitochondria have been demonstrated to be closely involved in tumorigenesis and progression, particularly DLBCL. Objective The purposes this study were identify prognostic mitochondria‐related genes (MRGs) DLBCL, develop a risk model based on MRGs machine learning algorithms. Methods Transcriptome profiles clinical information obtained from Gene Expression Omnibus (GEO) database. was defined using Least Absolute Shrinkage Selection Operator (Lasso) regression algorithm, its value further examined independent datasets. Patients stratified into two clusters scores, additionally nomogram generated score characteristics. pathway level, microenvironment, expression targeted therapy‐associated genes, response immunotherapy, drug sensitivity, somatic mutation status compared between clusters. Results Eighteen (DNM1L, PUSL1, CHCHD4, COX7A1, CPT1A, CYP27A1, POLDIP2, PCK2, MRPL2, PDK3, PDK4, MARC2, ACSM3, COA7, THNSL1, ATAD3B, C15orf48, TOMM70A) identified construct model. Remarkable discrepancies observed groups. high‐risk group had shorter overall survival, less immune infiltration, lower CD20 higher PD‐L1 than low‐risk group. Distinct responses immunotherapy predictive IC50 values found Conclusions We established novel signature by which also outstanding tumor microenvironment therapies.

Language: Английский

Citations

0
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
Apoptosis-inducing effects of aqueous extract of Eleutherococcus senticosus on non-small cell lung cancer cell proliferation DOI Creative Commons

Xiaolan Kou,

Yufeng Li, Lei Wang

et al.

CHINESE JOURNAL OF ANALYTICAL CHEMISTRY (CHINESE VERSION), Journal Year: 2025, Volume and Issue: unknown, P. 100510 - 100510

Published: Feb. 1, 2025

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
BMAL1 attenuates intervertebral disc degeneration by activating the SIRT1/PGC-1α pathway: evidence from vitro studies DOI Creative Commons
Peiming Sang, Yanyan Ma, Xie Zhang

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 20, 2025

To explore the potential effects and corresponding mechanisms of brain muscle arnt-like protein-1 (BMAL1) on progression intervertebral disc degeneration (IVDD) in vitro studies. The expression BMAL1, SIRT1 PINK1 were evaluated by method siRNA/pcDNA immortalized nucleus pulposus (NP) cells. SIRT1/PGC-1α pathway was assessed. characteristics NP cell, containing activity density, level apoptosis, inflammatory response, reactive oxygen species (ROS), senescence, mitophagy evaluated. overexpression BMAL1 achieved with pcDNA3.1, PGC-1α increased, ROS, apoptosis senescence decreased, however, mitophagy, density cell enhanced. inhibites IVDD activating

Language: Английский

Citations

0
The development of pyridazinone-based andrographolide derivatives as anti-cancer agents with the ability of inhibiting the TFAP4/Wnt/β-catenin signaling pathway DOI
Hang Zhang, Zhihao Xu,

Zhengyu Xu

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108440 - 108440

Published: April 1, 2025

Language: Английский

Citations

0
Overcoming Fluorescence Loss in mEOS-based AAA+ Unfoldase Reporters Through Covalent Linkage DOI Creative Commons

Isabella R. Walter,

Baylee A. Smith,

Dominic Castanzo

et al.

Protein Expression and Purification, Journal Year: 2025, Volume and Issue: unknown, P. 106724 - 106724

Published: April 1, 2025

Recent work has demonstrated that the soluble photoconvertable fluorescent protein mEOS can be a reporter for AAA+ (ATPases Associated with diverse cellular Activities) unfoldase activity. Given many proteins process membrane proteins, we sought to adapt use substrates. However, direct genetic fusion of completely abolished fluorescence, severely limiting utility studying proteins. To circumvent this challenge, separately purified and multiple different degrons, including transmembrane domain. We then covalently linked degrons via Sortase. This innovative approach preserves fluorescence photoconversion, even upon linkage Together, offers broadly applicable platform study associated

Language: Английский

Citations

0
Black phosphorus-based nanoparticles induce liver cancer cell mitochondrial apoptosis and immune cell tumor infiltration for enhancing dendritic cell therapy DOI Creative Commons

Ke Liao,

Shang Chen,

Gun Yang

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(5), P. e27234 - e27234

Published: March 1, 2024

Cellular immunotherapy is a crucial aspect of current tumor immunotherapy, though it presents several challenges such as immune cell dysfunction, limited recognition neoantigens, and inadequate lymphocyte infiltration into the microenvironment. This study proposes novel approach utilizing combination dendritic (DC)-based cellular photothermal nanoadjuvant black phosphorus (BP) nanoparticles to overcome these challenges. A new platform called PLGA@BP-R848, which consists modifying poly-(lactic-co-glycolic acid) (PLGA) onto BP nanosheets loading adjuvant R848. The PLGA@BP-R848 demonstrated exceptional drug delivery release capabilities, well effect, biocompatibility, ability activate mitochondrial apoptotic pathway Blc-2-Bax-Cytochrome c-caspase-3 inhibit PI3K-AKT-mTOR signaling pathway. In hepatocellular carcinoma mouse model, binding cells primed with GPC3 peptides, successfully induced systemic anti-tumor response. bolster tumors induce cancer apoptosis. synergistic therapy involving effectively suppressed growth, facilitated formation tertiary lymphatic structures (TLS) in tumors. using nanoadjuvants advance antitumor effect DCs therapy.

Language: Английский

Citations

3
Lysosome-Mitochondria Cascade Targeting Nanoparticle Drives Robust Pyroptosis for Cancer Immunotherapy DOI
Jianxiong Liu,

Yue Yan,

Yimeng Zhang

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 5, 2024

The subcellular distribution of cargoes plays a crucial role in determining cell fate and therapeutic efficacy. However, achieving the precise delivery therapeutics to specific intracellular targets remains significant challenge. Here, we present trimodular acid/enzyme-gated nanoplatform (TAEN) that undergoes disassembly within acidic endosomes then is cleaved by lysosomal cathepsin B facilitate efficient targeted transport released into mitochondria compartments. By utilizing this nanovehicle, successfully achieve selective sorting photosensitizer molecules with colocalization coefficient up 0.98, leading generation reactive oxygen species stress specifically for potent pyroptosis-based cancer therapy. induction mitochondrial triggers intrinsic apoptotic pathway as well caspase-3/gasdermin-E (GSDME) cascade, resulting an enhanced killing efficacy nearly 2 orders magnitude compared stress. Furthermore, due its superior capability stimulate both innate adaptive immune responses, our mitochondria-sorted nanophotosensitizer exhibits robust antitumor multiple tumor-bearing mice models. This study not only provides insights engineering nanomedicines but also offers valuable toolkit advanced research field nanobiology at resolution.

Language: Английский

Citations

3