Mitochondrial (dys) function: a double edge sword in cell stress response DOI Creative Commons
Nicoletta Guaragnella,

Maria Antonietta Di Noia,

Alessandro Primavera

и другие.

Frontiers in Cell Death, Год журнала: 2024, Номер 3

Опубликована: Дек. 18, 2024

Mitochondria are multifaceted organelles acting as energy, metabolic and signaling hubs in the cells. They play a central role biological processes aimed at maintaining cell homeostasis regulating fate upon changing environments. Alterations mitochondrial functions can affect stress response through different mechanisms, leading to adaptation or death. In this perspective, we focus on communication its relevance for cytoprotective strategies controlling synthesis, degradation recycling processes. The advantage of using yeast model organism improving our understanding molecular mechanisms behind responses dysfunction is described. New challenges studying interplay between retrograde autophagy/mitophagy pathways highlighted.

Язык: Английский

Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders DOI Creative Commons
Guangming Zhang,

Huayuan Wei,

Anliu Zhao

и другие.

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Фев. 7, 2025

Mitochondrial dysfunction is a pivotal instigator of neuroinflammation, with mitochondrial DNA (mtDNA) leakage as critical intermediary. This review delineates the intricate pathways leading to mtDNA release, which include membrane permeabilization, vesicular trafficking, disruption homeostatic regulation, and abnormalities in dynamics. The escaped activates cytosolic sensors, especially cyclic gmp-amp synthase (cGAS) signalling inflammasome, initiating neuroinflammatory cascades via pathways, exacerbating spectrum neurological pathologies. therapeutic promise targeting discussed detail, underscoring necessity for multifaceted strategy that encompasses preservation homeostasis, prevention leakage, reestablishment dynamics, inhibition activation sensors. Advancing our understanding complex interplay between neuroinflammation imperative developing precision interventions disorders.

Язык: Английский

Процитировано

3
Homeostasis control in health and disease by the unfolded protein response DOI
Diego Acosta‐Alvear, Jonathan M. Harnoss, Peter Walter

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 5, 2024

Язык: Английский

Процитировано

13
Adenosine deaminase and deoxyadenosine regulate intracellular immune response in C. elegans DOI Creative Commons
Nicole Wernet, Eillen Tecle,

Mario Bardan Sarmiento

и другие.

iScience, Год журнала: 2025, Номер 28(3), С. 111950 - 111950

Опубликована: Фев. 4, 2025

Adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) are enzymes in the salvage pathway, which recycles purines to meet cellular demands. Mutations of these humans cause inflammatory immunodeficiency syndromes, but mechanisms not well understood. Prior work nematode Caenorhabditis elegans demonstrated that loss PNP ortholog PNP-1 induced an immune response called intracellular pathogen (IPR). Here, we show enzyme upstream ADAH-1 (ADA homolog) also induces IPR promotes resistance against pathogens. Unlike PNP-1, is essential for organismal development. Importantly, find supplementation deoxyadenosine, a substrate ADA, pathogens C. elegans, finding extend human cells. Thus, mutations ADA induce innate immunity through increased phenomenon conserved from humans.

Язык: Английский

Процитировано

1
Analysis of environmental pollutant Bisphenol F elicited prostate injury targets and underlying mechanisms through network toxicology, molecular docking, and multi-level bioinformatics data integration DOI

Shujun Huang

Toxicology, Год журнала: 2024, Номер 506, С. 153847 - 153847

Опубликована: Июнь 2, 2024

Язык: Английский

Процитировано

5
Aging-Associated Modulation of UFMylation Impairs Proteostasis in C. elegans DOI Creative Commons
Ehud Cohen,

Reut Bruck-Haimson,

Hana Boocholez

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

Abstract The attachment of Post-Translational Modifications (PTMs) to proteins plays key roles in the regulation activity and stability various proteins. Here we utilized nematode Caenorhabditis elegans test whether UFMylation, a PTM that was found be essential for biological functions, is involved aging protein homeostasis (proteostasis). Our results indicate lowering UFMylation extends lifespan mitigates toxicity aggregative underlie development neurodegenerative disorders humans. Mass spectrometric analysis unveiled aging-regulating proteins, including components nucleolar FIB-1-NOL-56 complex germline resident CAR-1 CGH-1, governs proteostasis across tissues. Functional analyses proteostasis-regulating transcription factors DAF-16 SKN-1 are crucial counter proteotoxic effect reduced which mediated by rate aggregation enhanced degradation. These insights highlight important PTMs point at research directions new therapies disorders.

Язык: Английский

Процитировано

0
Dihydroartemisinin inhibits ATP6 activity, reduces energy metabolism of hepatocellular carcinoma cells, promotes apoptosis and inhibits metastasis via CANX DOI Open Access
Jiang Chang,

Qingzhuang Yang,

Xiangwei Liu

и другие.

Oncology Letters, Год журнала: 2024, Номер 28(4)

Опубликована: Авг. 2, 2024

Dihydroartemisinin (DHA) may inhibit the migration and invasion of liver cancer cells by reducing ATP synthase production (specifically ATP1A1 ATP5H) through calcium/calmodulin dependent protein kinase 2/solute carrier family 8 member B1 signaling pathway. However, it is unclear whether DHA regulates activity modulating other calcium ion signals to energy metabolism transfer hepatocellular carcinoma (HCC) cells. Using Gene Expression Profiling Interactive Analysis database, a search for specific expression genes in tissues was performed. Human HCC HuH-7 Li-7 were used produce CANX overexpression small interfering RNA cell models. The study assessed changes proliferation, apoptosis, invasion. Reactive oxygen species production, mitochondrial membrane potential (JC-1), NAD

Язык: Английский

Процитировано

2
Glomerular Elasticity and Gene Expression Patterns Define Two Phases of Alport Nephropathy DOI Open Access
Joon‐Ho Yoon, Zhenan Liu,

Mathew O. Alaba

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 29, 2024

Abstract Objectives To understand the early stages if Alport nephropathy, we characterize structural, functional, and biophysical properties of glomerular capillaries podocytes in Col4α3 -/- mice, analyze kidney cortex transcriptional profiles at three time points, investigate effects ER stress mitigation by TUDCA on these parameters. We use human FSGS associated genes to identify molecular pathways rescued TUDCA. Findings define a disease progression timeline mice. Podocyte injury is evident 3 months, with glomeruli reaching maximum deformability 4 40% loss, followed progressive capillary stiffening, increasing proteinuria, reduced renal function, inflammatory infiltrates, fibrosis from months 7. RNA sequencing 2, 4, 7 reveals increased cytokine chemokine signaling, matrix cell injury, activation TNF pathway similar NEPTUNE cohorts. These features are suppressed Conclusions two phases nephropathy. The first characterized podocytopathy, accelerated podocyte second wall stiffening profibrotic activation. Disease suppression treatment identifies potential therapeutic targets for treating related nephropathies.

Язык: Английский

Процитировано

0
James German and the Quest to Understand Human RECQ Helicase Deficiencies DOI Creative Commons
Raymond J. Monnat

Cells, Год журнала: 2024, Номер 13(13), С. 1077 - 1077

Опубликована: Июнь 21, 2024

James German's work to establish the natural history and cancer risk associated with Bloom syndrome (BS) has had a strong influence on generation of scientists clinicians working understand other RECQ deficiencies heritable predisposition syndromes. I summarize by us others below, inspired precedents BS, compare BS deficiency syndromes focus Werner (WS). What we know, unanswered questions new opportunities are discussed, as potential ways treat or modify WS-associated disease mechanisms pathways.

Язык: Английский

Процитировано

0
Mitochondrial Quality Control in Alzheimer’s Disease: Insights from Caenorhabditis elegans Models DOI Creative Commons
Upasana Ganguly, Trae Carroll, Keith Nehrke

и другие.

Antioxidants, Год журнала: 2024, Номер 13(11), С. 1343 - 1343

Опубликована: Ноя. 1, 2024

Alzheimer's disease (AD) is a complex neurodegenerative disorder that classically defined by the extracellular deposition of senile plaques rich in amyloid-beta (Aβ) protein and intracellular accumulation neurofibrillary tangles (NFTs) are aberrantly modified tau protein. In addition to aggregative proteostatic abnormalities, neurons affected AD also frequently possess dysfunctional mitochondria disrupted mitochondrial maintenance, such as inability eliminate damaged via mitophagy. Decades have been spent interrogating etiopathogenesis AD, contributions from model organism research aided developing more fundamental understanding molecular dysfunction caused Aβ toxic aggregates. The soil nematode

Язык: Английский

Процитировано

0
Mitochondrial (dys) function: a double edge sword in cell stress response DOI Creative Commons
Nicoletta Guaragnella,

Maria Antonietta Di Noia,

Alessandro Primavera

и другие.

Frontiers in Cell Death, Год журнала: 2024, Номер 3

Опубликована: Дек. 18, 2024

Mitochondria are multifaceted organelles acting as energy, metabolic and signaling hubs in the cells. They play a central role biological processes aimed at maintaining cell homeostasis regulating fate upon changing environments. Alterations mitochondrial functions can affect stress response through different mechanisms, leading to adaptation or death. In this perspective, we focus on communication its relevance for cytoprotective strategies controlling synthesis, degradation recycling processes. The advantage of using yeast model organism improving our understanding molecular mechanisms behind responses dysfunction is described. New challenges studying interplay between retrograde autophagy/mitophagy pathways highlighted.

Язык: Английский

Процитировано

0