Action and therapeutic targets of folliculin interacting protein 1: a novel signaling mechanism in redox regulation DOI Creative Commons

Qingzhi Ran,

Aoshuang Li,

Bo Yao

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Март 12, 2025

Rapid activation of adenosine monophosphate-activated protein kinase (AMPK) induces phosphorylation mitochondrial-associated proteins, a process by which phosphate groups are added to regulate mitochondrial function, thereby modulating energy metabolism, triggering an acute metabolic response, and sustaining adaptation through transcriptional regulation. AMPK directly phosphorylates folliculin interacting 1 (FNIP1), leading the nuclear translocation transcription factor EB (TFEB) in response functions. While function is tightly linked finely-tuned energy-sensing mobility, FNIP1 plays critical roles glucose transport sensing, autophagy, cellular stress muscle fiber contraction. Consequently, emerges as promising novel target for addressing aberrant metabolism. Recent evidence indicates that implicated biology various pathways, including AMPK, mTOR, ubiquitination, oxidative responses, skeletal Nonetheless, there dearth literature discussing physiological mechanism action therapeutic target. This review outlines how regulates metabolic-related signaling pathways enzyme activities, such catalytic activity enzymes, homeostasis products, controlling fate different contexts. Our focus will be on elucidating these metabolite-mediated processes inflammatory diseases.

Язык: Английский

Mechanisms and roles of membrane-anchored ATG8s DOI Creative Commons

Soo-Kyeong Lee,

Sang‐Won Park,

Deok‐Jin Jang

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Янв. 28, 2025

Autophagy-related protein 8 (ATG8) family proteins, including LC3 and GABARAP subfamilies, are pivotal in canonical autophagy, driving autophagosome formation, cargo selection, lysosomal fusion. However, recent studies have identified non-canonical roles for lipidated ATG8 processes such as LC3-associated phagocytosis (LAP), endocytosis (LANDO), ATG8-mediated secretory autophagy. These pathways expand ATG8’s functional repertoire immune regulation, membrane repair, pathogen clearance, becomes conjugated to single-membrane structures (e.g., phagosomes lysosomes). This review examines the molecular mechanisms of lipidation, focusing on its selective conjugation phosphatidylethanolamine (PE) autophagy phosphatidylserine (PS) CASM. We highlight LIR-based probes LC3/GABARAP-specific deconjugases critical tools that allow precise tracking manipulation autophagic non-autophagic contexts. advancements hold therapeutic promise treating autophagy-related diseases, cancer neurodegenerative disorders, by targeting ATG8-driven maintain cellular homeostasis.

Язык: Английский

Процитировано

1
Lysosomal Quality Control DOI Creative Commons
Dominic Henn, Xi Yang, Ming Li

и другие.

Autophagy, Год журнала: 2025, Номер unknown

Опубликована: Фев. 19, 2025

Healthy cells need functional lysosomes to degrade cargo delivered by autophagy and endocytosis. Defective can lead severe conditions such as lysosomal storage diseases (LSDs) neurodegeneration. To maintain lysosome integrity functionality, have evolved multiple quality control pathways corresponding different types of stress damage. These be divided into five levels: regulation, reformation, repair, removal, replacement. The levels often work together the network. This review summarizes discusses less-studied area membrane protein regulation degradation, highlighting key unanswered questions in field.

Язык: Английский

Процитировано

1
The spectrum of lysosomal stress and damage responses: from mechanosensing to inflammation DOI Creative Commons
Ori Scott, Ekambir Saran, Spencer A. Freeman

и другие.

EMBO Reports, Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

Abstract Cells and tissues turn over their aged damaged components in order to adapt a changing environment maintain homeostasis. These functions rely on lysosomes, dynamic heterogeneous organelles that play essential roles nutrient redistribution, metabolism, signaling, gene regulation, plasma membrane repair, immunity. Because of metabolic fluctuations pathogenic threats, lysosomes must the short long term functionality. In response such challenges, deploy variety mechanisms prevent breaching escape contents, including pathogen-associated molecules hydrolases. While transient permeabilization lysosomal can have acute beneficial effects, supporting inflammation antigen cross-presentation, sustained or repeated perforations adverse transcriptional consequences lead cell death. This review outlines factors contributing stress damage perception, as well remedial processes aimed at addressing disruptions. We conclude plays widespread human physiology pathology, understanding manipulation which open door novel therapeutic strategies.

Язык: Английский

Процитировано

1
Cellular homeostatic responses to lysosomal damage DOI
Jingyue Jia, Suttinee Poolsup, Jaime Salinas-Chavira

и другие.

Trends in Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

1
Lysosomes: guardians and healers within cells- multifaceted perspective and outlook from injury repair to disease treatment DOI Creative Commons
Jichao Bi, Yue‐Li Sun,

Meihua Guo

и другие.

Cancer Cell International, Год журнала: 2025, Номер 25(1)

Опубликована: Апрель 9, 2025

Lysosomes, as crucial organelles within cells, carry out diverse biological functions such waste degradation, regulation of the cellular environment, and precise control cell signaling. This paper reviews core structural characteristics lysosomes, delves into current research status lysosomes damage repair mechanisms. Subsequently, we explore in depth close association between various diseases, including but not limited to age-related chronic neuro-degenerative tumors, inflammation, immune imbalance. Additionally, also provide a detailed discussion application lysosome-targeted substances field regenerative medicine, especially enormous potential demonstrated key areas stem therapy, myocardial repair. Though integration multidisciplinary efforts, believe that mechanisms will demonstrate even greater value disease treatment medicine.

Язык: Английский

Процитировано

1
Calcium signaling from damaged lysosomes induces cytoprotective stress granules DOI Creative Commons

Jacob Duran,

Jaime Salinas-Chavira,

Rui Ping Wheaton

и другие.

The EMBO Journal, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 12, 2024

Abstract Lysosomal damage induces stress granule (SG) formation. However, the importance of SGs in determining cell fate and precise mechanisms that mediate SG formation response to lysosomal remain unclear. Here, we describe a novel calcium-dependent pathway controlling formation, which promotes survival during damage. Mechanistically, calcium-activated protein ALIX transduces signals by eIF2α phosphorylation after sensing calcium leakage. enhances promoting association between PKR its activator PACT, with galectin-3 inhibiting this interaction; these regulatory events occur on damaged lysosomes. We further find plays crucial role upon caused factors such as SARS-CoV-2 ORF3a , adenovirus, malarial pigment, proteopathic tau, or environmental hazards. Collectively, data provide insights into mechanism implicate it diseases associated lysosomes SGs.

Язык: Английский

Процитировано

8
Spatiotemporal proteomic profiling of cellular responses to NLRP3 agonists DOI Creative Commons
Louis Hollingsworth,

Priya Veeraraghavan,

João A. Paulo

и другие.

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

Опубликована: Апрель 20, 2024

ABSTRACT Nucleotide-binding domain and leucine-rich repeat pyrin-domain containing protein 3 (NLRP3) is an innate immune sensor that forms inflammasome in response to various cellular stressors. Gain-of-function mutations NLRP3 cause autoinflammatory diseases signalling itself exacerbates the pathogenesis of many other human diseases. Despite considerable therapeutic interest, primary drivers activation remain controversial due diverse array signals are integrated through NLRP3. Here, we mapped subcellular proteome changes lysosomes, mitochondrion, EEA1-positive endosomes, Golgi caused by agonists nigericin CL097. We identified several common disruptions retrograde trafficking pathways, including COPI Shiga toxin-related transport, line with recent studies. further characterized mouse throughout its using temporal proximity proteomics, which supports a model recruitment endosomes during activation. Collectively, these findings provide additional granularity our understanding molecular events driving serve as valuable resource for cell biological research. have made proteomics data accessible open-access Shiny browser facilitate future research within community, available at: https://harperlab.connect.hms.harvard.edu/inflame/ . will display anonymous peer review this manuscript on pubpub.org ( https://harperlab.pubpub.org/pub/nlrp3/ ) rather than traditional journal. Moreover, invite community feedback pubpub version manuscript, address criticisms accordingly.

Язык: Английский

Процитировано

5
Polarity-dependent expression and localization of secretory glucoamylase mRNA in filamentous fungal cells DOI Creative Commons

Yuki Morita,

Kaoru Takegawa, Brett M. Collins

и другие.

Microbiological Research, Год журнала: 2024, Номер 282, С. 127653 - 127653

Опубликована: Фев. 23, 2024

In multinuclear and multicellular filamentous fungi little is known about how mRNAs encoding secreted enzymes are transcribed localized spatiotemporally. To better understand this process we analyzed mRNA GlaA, a glucoamylase in large amounts by the industrial fungus Aspergillus oryzae, MS2 system, which can be visualized living cells. We found that glaA was significantly near hyphal tip septum, sites of protein secretion, polarity-dependent expression localization manners. also revealed exhibits long-range dynamics vicinity endoplasmic reticulum (ER) manner dependent on microtubule motor proteins kinesin-1 kinesin-3, but independent early endosomes. Moreover, elucidated although to stress granules (SGs) processing bodies (PBs) under high temperature, not seen ER stress, suggesting there different regulatory mechanisms SG PB temperature stress. Collectively, study uncovers dynamic mechanism secretory enzyme fungi.

Язык: Английский

Процитировано

4
Single-nucleus transcriptome unveils the role of ferroptosis in ischemic stroke DOI Creative Commons

Cheng-Long Shi,

Xiuli Han,

Jing-Ce Chen

и другие.

Heliyon, Год журнала: 2024, Номер 10(12), С. e32727 - e32727

Опубликована: Июнь 1, 2024

Multiple cell death pathways are involved in neuronal ischemic stroke (IS). However, the role of different types has not been elucidated. By analyzing three single-nucleus RNA sequencing (snRNA-seq) data IS, we first found that a variety programmed (PCD) -related genes were significantly changed types. Based on machine learning and virtual gene knockout, ferroptosis related genes, ferritin heavy chain 1 (Fth1) light (Ftl1), play key IS. Ftl1 Fth1 can promote microglia activation, as well production inflammatory factors chemokines. Cell communication analysis showed activated could enhance chemotactic peripheral leukocyte infiltration, such macrophages neutrophils, through Spp1-Cd44 App-Cd74 signaling, thereby aggravating brain tissue damage. Furthermore, real‐time quantitative polymerase reaction (RT‐qPCR) P2ry12 Mef2c decreased oxygen-glucose deprivation (OGD) group, while Ftl1, Fth1, Apoe, Ctsb, Cd44 Cd74 increased OGD group. Collectively, our findings suggested targeted therapy against might improve state microglia, reduce infiltration immune cells inflammation, then injury mouse.

Язык: Английский

Процитировано

4
Membrane Atg8ylation, stress granule formation, and MTOR regulation during lysosomal damage DOI
Jingyue Jia, Fulong Wang, Zambarlal Bhujabal

и другие.

Autophagy, Год журнала: 2022, Номер 19(6), С. 1893 - 1895

Опубликована: Ноя. 17, 2022

The functions of mammalian Atg8 proteins (mATG8s) expand beyond canonical autophagy and include processes collectively referred to as Atg8ylation. Global modulation protein synthesis under stress conditions is governed by MTOR liquid-liquid phase separated condensates containing ribonucleoprotein particles known granules (SGs). We report that lysosomal damage induces SGs acting a hitherto unappreciated inhibitor translation via EIF2A/eIF2α phosphorylation while favoring an ATF4-dependent integrated response. are induced lysosome-damaging agents, SARS-CoV-2 open reading frame 3a (ORF3a) expression, Mycobacterium tuberculosis infection, exposure proteopathic MAPT/tau. Proteomic studies revealed recruitment damaged lysosomes the core SG NUFIP2 G3BP1 along with GABARAPs mATG8 family. these independent or autophagy. interact directly whereas Atg8ylation needed for their lysosomes. At lysosome, contributes inactivation together LGALS8 (galectin 8) Ragulator-RRAGA-RRAGB complex. separable in formation vis-a-vis role GABARAP Thus, cells employ membrane control coordinate responses damage.Abbreviations: Atg8: related 8; ATG: related; ATF4: activating transcription factor 4; EIF2A/eIF2α: eukaryotic initiation 2A; GABARAP: GABA type A receptor-associated protein; G3BP1: G3BP granule assembly 1; LLOMe: L-leucyl-L-leucine methyl ester; LysoIP: lysosome immunopurification; mRNA: messenger ribonucleic acid; MTOR: mechanistic target rapamycin kinase; NUFIP2: nuclear FMR1 interacting 2; ORF3a: SARS-CoV-2: severe acute respiratory syndrome coronavirus SG: granule; TIA1: TIA1 cytotoxic associated RNA binding protein.

Язык: Английский

Процитировано

17