Trafficking to the lysosome: HOPS paves the way DOI Creative Commons
Jan van der Beek, Judith Klumperman

Current Opinion in Cell Biology, Journal Year: 2025, Volume and Issue: 94, P. 102515 - 102515

Published: April 21, 2025

The endo-lysosomal system plays a crucial role in cellular homeostasis by continuously turning over organelles, proteins, and other cargo of intra- or extracellular origin. Moreover, it senses the nutrient status within cell can ignite responses activating repressing signaling pathways. To enable these roles, lysosomes are fueled biosynthetic pathway receive for degradation endocytosis autophagy. Tight regulation coordination distinct trafficking pathways to critical health. In this review, we explore how converge at late stages highlight HOPS complex as unifying gatekeeper lysosome.

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

84
The emerging roles of miRNA-mediated autophagy in ovarian cancer DOI Creative Commons

Yamin Ding,

Xuan Huang, Tuo Ji

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(5)

Published: May 3, 2024

Abstract Ovarian cancer is one of the common tumors female reproductive organs. It has a high mortality rate, highly heterogeneous, and early detection primary prevention are very complex. Autophagy cellular process in which cytoplasmic substrates targeted for degradation lysosomes through membrane structures called autophagosomes. The periodic elimination damaged, aged, redundant molecules or organelles sequential translation between amino acids proteins by two biological processes, protein synthesis, autophagic degradation, helps maintain homeostasis. A growing number studies have found that autophagy plays key regulatory role ovarian cancer. Interestingly, microRNAs regulate gene expression at posttranscriptional level thus can development progression regulation Certain miRNAs recently emerged as important regulators autophagy-related cells. Moreover, miRNA analysis now identified sea aberrantly expressed tissues affect In addition, plasma stromal cells tumor patients genes be used biomarkers progression. This review focuses on potential significance miRNA-regulated diagnosis treatment

Language: Английский

Citations

11
Pharmacological induction of autophagy reduces inflammation in macrophages by degrading immunoproteasome subunits DOI Creative Commons

Jiao Zhou,

Chunxia Li,

Meng Kai Lü

et al.

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(3), P. e3002537 - e3002537

Published: March 6, 2024

Defective autophagy is linked to proinflammatory diseases. However, the mechanisms by which limits inflammation remain elusive. Here, we found that pan-FGFR inhibitor LY2874455 efficiently activated and suppressed expression of factors in macrophages stimulated lipopolysaccharide (LPS). Multiplex proteomic profiling identified immunoproteasome, a specific isoform 20s constitutive proteasome, as substrate degraded selective autophagy. SQSTM1/p62 was be autophagy-related receptor mediated this degradation. Autophagy deficiency or p62 knockdown blocked effects LY2874455, leading accumulation immunoproteasomes increases inflammatory reactions. Expression autophagy-deficient could reversed immunoproteasome inhibitors, confirming pivotal role turnover autophagy-mediated suppression on factors. In mice, protected against LPS-induced acute lung injury dextran sulfate sodium (DSS)-induced colitis caused low levels cytokines immunoproteasomes. These findings suggested key regulator signaling via innate immune system.

Language: Английский

Citations

9
Molecular Mechanism of Autophagosome–Lysosome Fusion in Mammalian Cells DOI Creative Commons
Po‐Yuan Ke

Cells, Journal Year: 2024, Volume and Issue: 13(6), P. 500 - 500

Published: March 13, 2024

In eukaryotes, targeting intracellular components for lysosomal degradation by autophagy represents a catabolic process that evolutionarily regulates cellular homeostasis. The successful completion of initiates the engulfment cytoplasmic materials within double-membrane autophagosomes and subsequent delivery to autolysosomes acidic proteases. formation relies on precise fusion with lysosomes. recent decades, numerous studies have provided insights into molecular regulation autophagosome–lysosome fusion. this review, an overview molecules function in lysosomes is provided. Moreover, mechanism underlying how these functional regulate summarized.

Language: Английский

Citations

9
Berberine Alleviates Ischemic Brain Injury by Enhancing Autophagic Flux via Facilitation of TFEB Nuclear Translocation DOI

Yi-Li Liu,

Tao Guo,

Yong-Jie Zhang

et al.

The American Journal of Chinese Medicine, Journal Year: 2024, Volume and Issue: 52(01), P. 231 - 252

Published: Jan. 1, 2024

Berberine has been demonstrated to alleviate cerebral ischemia/reperfusion injury, but its neuroprotective mechanism yet be understood. Studies have indicated that ischemic neuronal damage was frequently driven by autophagic/lysosomal dysfunction, which could restored boosting transcription factor EB (TFEB) nuclear translocation. Therefore, this study investigated the pharmacological effects of berberine on TFEB-regulated signaling in neurons after stroke. A rat model stroke and a ischemia HT22 cells were prepared using middle artery occlusion (MCAO) oxygen-glucose deprivation (OGD), respectively. pre-administered at dose 100[Formula: see text]mg/kg/d for three days rats 90[Formula: text][Formula: text]M 12[Formula: text]h. 24[Formula: text]h MCAO 2[Formula: OGD, penumbral tissues OGD obtained detect cytoplasmic TFEB, key proteins pathway examined western blot immunofluorescence, Meanwhile, neuron survival, infarct volume, neurological deficits assessed evaluate therapeutic efficacy. The results showed prominently facilitated TFEB translocation, as increased expression well cells. Consequently, both autophagic activity lysosomal capacity simultaneously augmented injury. However, berberine-conferred neuroprotection greatly counteracted inhibitor Bafilomycin A1 (Baf-A1). autophagy 3-Methyladenine (3-MA) also slightly neutralized effect ameliorating dysfunction. Our suggests berberine-induced against is elicited enhancing flux via facilitation translocation neurons.

Language: Английский

Citations

8
Autophagy and neurodegeneration: Unraveling the role of C9ORF72 in the regulation of autophagy and its relationship to ALS-FTD pathology DOI Creative Commons

Rim Diab,

Federica Pilotto, Smita Saxena

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: March 16, 2023

The proper functioning of the cell clearance machinery is critical for neuronal health within central nervous system (CNS). In normal physiological conditions, actively involved in elimination misfolded and toxic proteins throughout lifetime an organism. highly conserved regulated pathway autophagy one important processes preventing neutralizing pathogenic buildup that could eventually lead to development neurodegenerative diseases (NDs) such as Alzheimer's disease or Amyotrophic lateral sclerosis (ALS). most common genetic cause ALS frontotemporal dementia (FTD) a hexanucleotide expansion consisting GGGGCC (G4C2) repeats chromosome 9 open reading frame 72 gene (C9ORF72). These abnormally expanded have been implicated leading three main modes pathology: loss function C9ORF72 protein, generation RNA foci, production dipeptide repeat (DPRs). this review, we discuss role autophagy-lysosome (ALP), present recent research deciphering how dysfunction ALP synergizes with haploinsufficiency, which together gain mechanisms involving expansions DPRs, drive process. This review delves further into interactions RAB endosomal/lysosomal trafficking, their regulating various steps lysosomal pathways. Lastly, aims provide framework investigations C9ORF72-linked ALS-FTD well other diseases.

Language: Английский

Citations

18
Recent progresses in the late stages of autophagy DOI Creative Commons

Yanyan Zhu,

Fengping Liu,

Fenglei Jian

et al.

Cell Insight, Journal Year: 2024, Volume and Issue: 3(2), P. 100152 - 100152

Published: Feb. 8, 2024

Autophagy, a lysosome-dependent degradation process, plays crucial role in maintaining cell homeostasis. It serves as vital mechanism for adapting to stress and ensuring intracellular quality control. Autophagy deficiencies or defects are linked numerous human disorders, especially those associated with neuronal degeneration metabolic diseases. Yoshinori Ohsumi was honored the Nobel Prize Physiology Medicine 2016 his groundbreaking discoveries regarding autophagy mechanisms. Over past few decades, research has predominantly concentrated on early stages of autophagy, relatively limited attention given late stages. Nevertheless, recent studies have witnessed substantial advancements understanding molecular intricacies stages, which follows autophagosome formation. This review provides comprehensive summary progresses comprehending mechanisms autophagy.

Language: Английский

Citations

7
Enhancing endometrial receptivity: the roles of human chorionic gonadotropin in autophagy and apoptosis regulation in endometrial stromal cells DOI Creative Commons
B. Wang, Mingxia Gao,

Ying Yao

et al.

Reproductive Biology and Endocrinology, Journal Year: 2024, Volume and Issue: 22(1)

Published: April 4, 2024

Abstract Inadequate endometrial receptivity often results in embryo implantation failure and miscarriage. Human chorionic gonadotropin (hCG) is a key signaling molecule secreted during early embryonic development, which regulates maternal interface promotes implantation. This study aimed to examine the impact of hCG on its underlying mechanisms. An exploratory was designed, samples were obtained from women diagnosed with simple tubal infertility or male factor infertile ( n = 12) recurrent (RIF, 10). Using reverse transcription-quantitative PCR western blotting, luteinizing hormone (LH)/hCG receptor (LHCGR) levels autophagy detected tissues. Subsequently, primary stromal cells (ESCs) isolated these control groups treated presence LHCGR markers (HOXA10, ITGB3, FOXO1, LIF, L-selectin ligand) autophagy-related factors (Beclin1, LC3, P62). The findings revealed that expressions factors, LHCGR, LC3 reduced tissues RIF compared group, whereas expression P62 elevated. administration ESCs specifically activated stimulating an increase production HOXA10, LIF ligands. Furthermore, when exposed 0.1 IU/mL for 72 h, Beclin1 increased within decreased. Moreover, apoptotic Bax Bcl-2 declined. However, small interfering RNA used knock down less capable controlling molecules ESCs. In addition, stimulation enhanced phosphorylation ERK1/2 mTOR proteins. These suggest exhibit lower compromised function their Thus, hCG/LHCGR could potentially improve by modulating apoptosis.

Language: Английский

Citations

7
Acteoside delays the fibrosis process of diabetic nephropathy by anti-oxidation and regulating the autophagy-lysosome pathway DOI
Mengqi Zhou,

Shujiao Zhang,

Xuehui Bai

et al.

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 978, P. 176715 - 176715

Published: June 7, 2024

Language: Английский

Citations

6
Autophagy modulation in cancer therapy: Challenges coexist with opportunities DOI
Yongya Wu,

Aoxue Wang,

Guotai Feng

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 276, P. 116688 - 116688

Published: July 17, 2024

Language: Английский

Citations

5