The landscape of immune cell infiltration and potential biomarkers in intervertebral disc degeneration DOI Creative Commons

Yuanhao Wang,

Bingtao Hu,

Lijun Tian

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Авг. 8, 2024

Abstract Background Immune cell infiltration has been found to be strongly associated with the occurrence and progression of intervertebral disc degeneration (IDD), discs (IVDs) are immune-privileged organs. This research aimed identify novel targets for therapeutic intervention investigate significant physiological cellular mechanisms involved in immune processes IDD. Results CIBERSORT deconvolution analysis revealed that levels follicular helper T cells M2 macrophages were significantly increased during IDD, while resting mast decreased. WGCNA blue module was macrophage (positive correlation 0.87, P < 0.001), which genes, including VAMP8, TLR4, JUN, PLA2G4A, NMI, RORA, IFNGR1, IFNGR2, NINJ1, TNIP1, CD81, mainly enriched activation, myeloid leukocyte activation Toll-like receptor 4 signaling pathway. The proportion leukocytes IVD greatest on 14th day after puncture. Single-cell sequencing division degenerative into seven major types, annulus fibrosus cells, smooth muscle fibroblasts, macrophages, monocytes, vascular endothelial NP Jun, Cd81, Rora, Vamp8, Ninj1, Tnip1 expressed, western blotting results normal degenerated nucleus pulposus (NNP DNP) showed expression VAMP8 c-Jun 24 hours stimulation 50 ng/ml TNF-α. immunohistochemical an increase rats acupuncture. Conclusion acupuncture is a crucial time point cells. work first reveal linked Elevated confirmed both DNP punctured rat IVDs.

Язык: Английский

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

Cells, Год журнала: 2024, Номер 13(6), С. 500 - 500

Опубликована: Март 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.

Язык: Английский

Процитировано

9
Deacetylated SNAP47 recruits HOPS to facilitate autophagosome-lysosome fusion independent of STX17 DOI Creative Commons

Fenglei Jian,

Shen Wang,

Wenmin Tian

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 9, 2025

Autophagy, a conserved catabolic process implicated in diverse array of human diseases, requires efficient fusion between autophagosomes and lysosomes to function effectively. Recently, SNAP47 has been identified as key component the dual-purpose SNARE complex mediating autophagosome-lysosome both bulk selective autophagy. However, spatiotemporal regulatory mechanisms this remain unknown. In study, we found that undergoes acetylation followed by deacetylation during autophagy mitophagy. The status is regulated acetyltransferase CBP deacetylase HDAC2. Notably, dynamics differ mitophagy due distinct regulation on activity deacetylase. Acetylated inhibits indirectly impeding assembly. Mechanistically, deacetylated recruits HOPS components autophagic vacuoles independently STX17 STX17-SNAP47 interaction, while acetylated recruitment, consequently leading failure Taken together, our study uncovers acetylation-dependent mechanism governing modulating recruitment without involving STX17, SNAP47-STX17 interaction ternary formation.

Язык: Английский

Процитировано

1
Recent progresses in the late stages of autophagy DOI Creative Commons

Yanyan Zhu,

Fengping Liu,

Fenglei Jian

и другие.

Cell Insight, Год журнала: 2024, Номер 3(2), С. 100152 - 100152

Опубликована: Фев. 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.

Язык: Английский

Процитировано

7
Autophagy intersection: Unraveling the role of the SNARE complex in lysosomal fusion in Alzheimer's disease DOI Creative Commons
Siyu Li, Yangyang Wang, Kristina Xiao Liang

и другие.

Journal of Alzheimer s Disease, Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

Autophagy is a fundamental cellular process critical for maintaining neuronal health, particularly in the context of neurodegenerative diseases such as Alzheimer's disease (AD). This review explores intricate role SNARE complex fusion autophagosomes with lysosomes, crucial step autophagic flux. Disruptions this process, often resulting from aberrant function or impaired lysosomal acidification, contribute to pathological accumulation and lysosomes observed AD. We examine composition, regulation, interacting molecules complex, emphasizing its central autophagosome-lysosome fusion. Furthermore, we discuss potential impact specific protein mutations broader implications health progression. By elucidating molecular mechanisms underlying SNARE-mediated fusion, aim highlight therapeutic targets that could restore mitigate processes characteristic

Язык: Английский

Процитировано

0
Function of lamp2 Gene Response to Vibrio vulnificus Infection and LPS Stimulation in the Half-Smooth Tongue Sole (Cynoglossus semilaevis) DOI Open Access
Han Tian, Yufeng Liu, Mengchao Li

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 1999 - 1999

Опубликована: Фев. 25, 2025

Lysosome-associated membrane glycoproteins (LAMPs), including lysosomal protein 1 (Lamp1) and 2 (Lamp2), are involved in phagocytosis, chaperone-mediated autophagy (CMA), other pathways that interact with activity. However, the role of Lamp2 teleosts has not been clarified. In this study, we investigated functions lamp2 genes during Vibrio vulnificus infection. We achieved subcellular localization gene at cellular level performed overexpression RNA interference experiments followed by Lipopolysaccharides (LPS) stimulation to probe expression changes related genes. Ultrapathology analysis head-kidney revealed an increase lysosomes formation autophagosomal vesicles after V. infection, suggesting bind autophagosomes. The gene, encoding 401 amino acids Cynoglossus semilaevis, was constitutively expressed all examined tissues healthy half-smooth tongue sole, highest blood. A challenge test conducted assess response sole (Cynoglossus semilaevis) different concentrations vulnificus. results showed relative its genes-lc3, rab7, vamp8, atg14, stx17, snap29, ctsb, ctsd-varied time concentration gill, spleen, head-kidney, blood, liver, gut tissues. From experiments, it is hypothesized positively regulates lc3, negatively ctsd ctsb. Our findings provide new primary data for function sole., particularly regulating immune against

Язык: Английский

Процитировано

0
Oncogenic RAS induces a distinctive form of non-canonical autophagy mediated by the P38-ULK1-PI4KB axis DOI Creative Commons
Xiaojuan Wang, Shulin Li, Shiyin Lin

и другие.

Cell Research, Год журнала: 2025, Номер unknown

Опубликована: Март 7, 2025

Язык: Английский

Процитировано

0
MicroRNAs and lysosomal membrane proteins: Critical interactions in tumor progression and therapy DOI
Jiahao Xu, Shiqiang Liu, Yujie Jin

и другие.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2025, Номер unknown, С. 189303 - 189303

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Autophagy in adult stem cell homeostasis, aging, and disease therapy DOI Creative Commons
Ke Zhao,

Indigo T.C. Chan,

Erin H. Y. Tse

и другие.

Cell Regeneration, Год журнала: 2025, Номер 14(1)

Опубликована: Апрель 10, 2025

Abstract Autophagy is a crucial cellular process that facilitates the degradation of damaged organelles and protein aggregates, recycling components for energy production macromolecule synthesis. It plays an indispensable role in maintaining homeostasis. Over recent decades, research has increasingly focused on autophagy regulating adult stem cells (SCs). Studies suggest modulates various processes states SCs, including quiescence, proliferation, self-renewal, differentiation. The primary these contexts to sustain homeostasis, withstand stressors, supply energy. Notably, dysfunction SCs during aging correlated with decline autophagic activity, suggesting also involved SC- aging-associated disorders. Given diverse mediated by intricate mechanisms governing further essential elucidate both universal cell type-specific regulatory pathways autophagy. This review discusses Additionally, it summarizes relationship between SC autophagy, providing therapeutical insights into treating ameliorating diseases cancers, ultimately promoting longevity.

Язык: Английский

Процитировано

0
Overview of the Autophagy Pathways Associated with Infection DOI Open Access
Eunjin Park, Eun‐Kyeong Jo, Seungwha Paik

и другие.

Journal of Bacteriology and Virology, Год журнала: 2025, Номер 55(1), С. 10 - 25

Опубликована: Март 31, 2025

Язык: Английский

Процитировано

0
Migratory autolysosome disposal mitigates lysosome damage DOI
Takami Sho, Ying Li, Haifeng Jiao

и другие.

The Journal of Cell Biology, Год журнала: 2024, Номер 223(12)

Опубликована: Сен. 30, 2024

Lysosomes, essential for intracellular degradation and recycling, employ damage-control strategies such as lysophagy membrane repair mechanisms to maintain functionality cellular homeostasis. Our study unveils migratory autolysosome disposal (MAD), a response lysosomal damage where cells expel LAMP1-LC3 positive structures via exocytosis, requiring autophagy machinery, SNARE proteins, cell migration. This mechanism, crucial mitigating damage, underscores the role of migration in lysosome control facilitates release small extracellular vesicles, highlighting intricate relationship between migration, organelle quality control, vesicle release.

Язык: Английский

Процитировано

3