Endoplasmic reticulum stress and quality control in relation to cisplatin resistance in tumor cells DOI Creative Commons

Wentao Mu,

Zhi Yao,

Jianpeng Zhou

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: June 14, 2024

The endoplasmic reticulum (ER) is a crucial organelle that orchestrates key cellular functions like protein folding and lipid biosynthesis. However, it highly sensitive to disturbances lead ER stress. In response, the unfolded response (UPR) activates restore homeostasis, primarily through three sensors: IRE1, ATF6, PERK. ERAD autophagy are in mitigating stress, yet their dysregulation can accumulation of misfolded proteins. Cisplatin, commonly used chemotherapy drug, induces stress tumor cells, activating complex signaling pathways. Resistance cisplatin stems from reduced drug accumulation, activation DNA repair, anti-apoptotic mechanisms. Notably, cisplatin-induced dualistically affect promoting either survival or apoptosis, depending on context. for degrading proteins, whereas protect cells apoptosis enhance stress-induced apoptosis. interaction between resistance, ERAD, opens new avenues cancer treatment. Understanding these processes could innovative strategies overcome chemoresistance, potentially improving outcomes cisplatin-based treatments. This comprehensive review provides multifaceted perspective mechanisms implications therapy.

Language: Английский

Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology DOI
Carmine Settembre, Rushika M. Perera

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(3), P. 223 - 245

Published: Nov. 24, 2023

Language: Английский

Citations

88
Protein Misfolding and Aggregation in Proteinopathies: Causes, Mechanism and Cellular Response DOI Creative Commons

Mohammad Ajmal

Diseases, Journal Year: 2023, Volume and Issue: 11(1), P. 30 - 30

Published: Feb. 9, 2023

Proteins are central to life functions. Alterations in the structure of proteins reflected their function. Misfolded and aggregates present a significant risk cell. Cells have diverse but integrated network protection mechanisms. Streams misfolded that cells continuously exposed must be continually monitored by an elaborated molecular chaperones protein degradation factors control contain misfolding problems. Aggregation inhibition properties small molecules such as polyphenols important they possess other beneficial antioxidative, anti-inflammatory, pro-autophagic help neuroprotection. A candidate with desired features is for any possible treatment development aggregation diseases. There need study phenomenon so we can treat some worst kinds human ailments related aggregation.

Language: Английский

Citations

46
New insights into the role of mitochondrial dynamics in oxidative stress-induced diseases DOI Open Access
Sisi Chen, Qilong Li,

Hanjing Shi

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 178, P. 117084 - 117084

Published: Aug. 1, 2024

The accumulation of excess reactive oxygen species (ROS) can lead to oxidative stress (OS), which induce gene mutations, protein denaturation, and lipid peroxidation directly or indirectly. expression is reduced ATP level in cells, increased cytoplasmic Ca

Language: Английский

Citations

42
Two FAM134B isoforms differentially regulate ER dynamics during myogenesis DOI Creative Commons

Viviana Buonomo,

Kateryna Lohachova, Alessio Reggio

et al.

The EMBO Journal, Journal Year: 2025, Volume and Issue: 44(4), P. 1039 - 1073

Published: Jan. 6, 2025

Language: Английский

Citations

3
TMX4-driven LINC complex disassembly and asymmetric autophagy of the nuclear envelope upon acute ER stress DOI Creative Commons
Marika Kucińska, Juliette Fédry,

Carmela Galli

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 13, 2023

The endoplasmic reticulum (ER) is an organelle of nucleated cells that produces proteins, lipids and oligosaccharides. ER volume activity are increased upon induction unfolded protein responses (UPR) reduced activation ER-phagy programs. A specialized domain the ER, nuclear envelope (NE), protects cell genome with two juxtaposed lipid bilayers, inner outer membranes (INM ONM) separated by perinuclear space (PNS). Here we report expansion mammalian homeostatic perturbations results in TMX4 reductase-driven disassembly LINC complexes connecting INM ONM swelling. physiologic distance between restored, resolution stress, asymmetric autophagy NE, which involves LC3 lipidation machinery, receptor SEC62 direct capture ONM-derived vesicles degradative LAMP1/RAB7-positive endolysosomes a catabolic pathway mechanistically defined as micro-ONM-phagy.

Language: Английский

Citations

29
The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease DOI Creative Commons
Sarah X. Zhang, Josh J. Wang, Christopher R. Starr

et al.

Progress in Retinal and Eye Research, Journal Year: 2023, Volume and Issue: 98, P. 101231 - 101231

Published: Dec. 12, 2023

Language: Английский

Citations

23
The Epstein-Barr virus deubiquitinase BPLF1 regulates stress-induced ribosome UFMylation and reticulophagy DOI Creative Commons
Jiangnan Liu, Noémi Nagy, Carlos Ayala‐Torres

et al.

Autophagy, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 23

Published: Jan. 22, 2025

The synthesis of membrane and secreted proteins is safeguarded by an endoplasmic reticulum-associated ribosome quality control (ER-RQC) that promotes the disposal defective translation products proteasome or via a lysosome-dependent pathway involving degradation portions ER macroautophagy (reticulophagy). UFMylation RPL26 on ER-stalled ribosomes essential for activating ER-RQC reticulophagy. Here, we report viral deubiquitinase (vDUB) encoded in N-terminal domain Epstein-Barr virus (EBV) large tegument protein BPLF1 hinders stall at ER, stabilization substrates, inhibits vDUB did not act as de-UFMylase interfere with CYB5R3 UFL1 ligase. Instead, it copurified sucrose gradients abrogated ZNF598- LTN1-independent ubiquitination event required UFMylation. Physiological levels impaired productively EBV-infected cells, pointing to important role enzyme regulating allows efficient production infectious virus.

Language: Английский

Citations

1
Missense variants in GABAA receptor beta2 subunit disrupt receptor biogenesis and cause loss of function DOI Creative Commons
Xi Chen, Yajuan Wang, Ting‐Wei Mu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

Gamma-aminobutyric acid type A receptors (GABA Rs) are the major inhibitory neurotransmitter-gated channel in mammalian central nervous system. GABA Rs function as heteropentamers, typically composed of two α1, β2, and one γ2 subunits. Protein homeostasis between R folding, trafficking, assembly, degradation is critical to ensure normal physiological functions. Variants genes encoded for lead numerous neurological disorders, such genetic epilepsy with or without neurodevelopmental delay. While these variants associated severe clinical presentations epilepsy, molecular mechanisms driving disease remain be elucidated. In this study, we focused on four missense epilepsy-associated (EAVs) GABRB2 gene: Q209F210delinsH (c. 627_629del), R240T 719G>C), I246T 737T>C), I299S 896T>G). HEK293T cells exogenously expressing β2 exhibited significantly reduced GABA-induced peak chloride current, indicating their loss function. However, EAVs differed degree proteostasis deficiencies, including increased ER retention, compromised decreased protein stability, trafficking surface expression, leading most degradation. Collectively, results indicate that epilepsy-linked have debilitating effects early biogenesis subunit, causing misfolding, aggregation, rapid before it can assembled other subunits transported plasma membrane. Overall, our work offers crucial mechanistic insight into how specific impact maintenance Rs, which could facilitate development effective therapeutics by targeting trafficking-deficient variants.

Language: Английский

Citations

1
A triple-targeting and viscosity-sensitive fluorescence probe for visualization of liver injury and tumor models DOI
Lei Peng, Pengfei Wei, Chuan Dong

et al.

Sensors and Actuators B Chemical, Journal Year: 2025, Volume and Issue: unknown, P. 137614 - 137614

Published: March 1, 2025

Language: Английский

Citations

1
ER‐to‐lysosome‐associated degradation in a nutshell: mammalian, yeast, and plant ER‐phagy as induced by misfolded proteins DOI Creative Commons
Mikhail Rudinskiy, Maurizio Molinari

FEBS Letters, Journal Year: 2023, Volume and Issue: 597(15), P. 1928 - 1945

Published: June 1, 2023

Conserved catabolic pathways operate to remove aberrant polypeptides from the endoplasmic reticulum (ER), major biosynthetic organelle of eukaryotic cells. The best known are ER-associated degradation (ERAD) that control retrotranslocation terminally misfolded proteins across ER membrane for clearance by cytoplasmic ubiquitin/proteasome system. In this review, we catalog folding-defective mammalian, yeast, and plant fail engage ERAD machineries. We describe they rather segregate in subdomains eventually vesiculate. These ER-derived vesicles captured double autophagosomes, engulfed endolysosomes/vacuoles, or fused with degradative organelles clear cells their toxic cargo. client-specific, mechanistically diverse ER-phagy grouped under umbrella term ER-to-lysosome-associated description essay.

Language: Английский

Citations

21