S100A8/A9hi neutrophils induce mitochondrial dysfunction and PANoptosis in endothelial cells via mitochondrial complex I deficiency during sepsis DOI Creative Commons

Yanghanzhao Wang,

Yuxin Shi,

Yuwen Shao

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(6)

Published: June 28, 2024

Abstract S100a8/a9, largely released by polymorphonuclear neutrophils (PMNs), belongs to the S100 family of calcium-binding proteins and plays a role in variety inflammatory diseases. Although S100a8/a9 has been reported trigger endothelial cell apoptosis, mechanisms S100a8/a9-induced dysfunction during sepsis require in-depth research. We demonstrate that high expression levels suppress Ndufa3 mitochondrial complex I via downregulation Nrf1 expression. Mitochondrial deficiency contributes NAD + -dependent Sirt1 suppression, which induces disorders, including excessive fission blocked mitophagy, mtDNA from damaged mitochondria ultimately activates ZBP1-mediated PANoptosis cells. Moreover, based on comprehensive scRNA-seq bulk RNA-seq analyses, S100A8/A9 hi are closely associated with circulating count (a useful marker damage), S100A8 is an independent risk factor for poor prognosis patients.

Language: Английский

Autophagy and autophagy-related pathways in cancer DOI Open Access
Jayanta Debnath, Noor Gammoh, Kevin M. Ryan

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(8), P. 560 - 575

Published: March 2, 2023

Language: Английский

Citations

669
Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy DOI Creative Commons

Weitong Gao,

Yuqin Wang, Yang Zhou

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 20, 2022

Abstract In recent years, immunotherapy represented by immune checkpoint inhibitors (ICIs) has led to unprecedented breakthroughs in cancer treatment. However, the fact that many tumors respond poorly or even not ICIs, partly caused absence of tumor-infiltrating lymphocytes (TILs), significantly limits application ICIs. Converting these “cold” into “hot” may ICIs is an unsolved question immunotherapy. Since it a general characteristic cancers resist apoptosis, induction non-apoptotic regulated cell death (RCD) emerging as new treatment strategy. Recently, several studies have revealed interaction between RCD and antitumor immunity. Specifically, autophagy, ferroptosis, pyroptosis, necroptosis exhibit synergistic responses while possibly exerting inhibitory effects on responses. Thus, targeted therapies (inducers inhibitors) against combination with exert potent activity, resistant This review summarizes multilevel relationship immunity RCD, including necroptosis, potential targeting improve efficacy malignancy.

Language: Английский

Citations

600
Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer DOI Creative Commons
Qingfang Han, Wenjia Li, Kaishun Hu

et al.

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Nov. 1, 2022

Abstract Exosomes are well-known key mediators of intercellular communication and contribute to various physiological pathological processes. Their biogenesis involves four steps, including cargo sorting, MVB formation maturation, transport MVBs, fusion with the plasma membrane. Each process is modulated through competition or coordination multiple mechanisms, whereby diverse repertoires molecular cargos sorted into distinct subpopulations exosomes, resulting in high heterogeneity exosomes. Intriguingly, cancer cells exploit strategies, such as aberrant gene expression, posttranslational modifications, altered signaling pathways, regulate biogenesis, composition, eventually functions exosomes promote progression. Therefore, exosome biogenesis-targeted therapy being actively explored. In this review, we systematically summarize recent progress understanding machinery how it regulated context cancer. particular, highlight pharmacological targeting a promising therapeutic strategy.

Language: Английский

Citations

345
The emerging mechanisms and functions of microautophagy DOI
Liming Wang, Daniel J. Klionsky, Han‐Ming Shen

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 24(3), P. 186 - 203

Published: Sept. 12, 2022

Language: Английский

Citations

250
Autophagy in Alzheimer’s disease pathogenesis: Therapeutic potential and future perspectives DOI Creative Commons
Zhigang Zhang, Xifei Yang, You‐Qiang Song

et al.

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 72, P. 101464 - 101464

Published: Sept. 20, 2021

Alzheimer's disease (AD) is a complex neurodegenerative in the elderly and most common cause of human dementia. AD characterized by accumulation abnormal protein aggregates including amyloid plaques (composed beta-amyloid (Aβ) peptides) neurofibrillary tangles (formed hyper-phosphorylated tau protein). Synaptic plasticity, neuroinflammation, calcium signaling etc. also show dysfunction patients. Autophagy an evolutionarily conserved lysosome-dependent cellular event eukaryotes. It closely linked to modulation metabolism, through which damaged organelles mis-folded proteins are degraded then recycled maintain homeostasis. Accumulating evidence has shown that impaired autophagy contributes pathogenesis. In present review, we highlight role autophagy, bulk selective regulating metabolic circuits We discuss potential future perspectives autophagy-inducing strategies therapeutics.

Language: Английский

Citations

225
ORF3a of SARS-CoV-2 promotes lysosomal exocytosis-mediated viral egress DOI Creative Commons
Di Chen,

Qiaoxia Zheng,

Long Sun

et al.

Developmental Cell, Journal Year: 2021, Volume and Issue: 56(23), P. 3250 - 3263.e5

Published: Oct. 12, 2021

Language: Английский

Citations

156
The multifaceted role of autophagy in cancer DOI Open Access
Ryan C. Russell, Kun‐Liang Guan

The EMBO Journal, Journal Year: 2022, Volume and Issue: 41(13)

Published: May 10, 2022

Language: Английский

Citations

130
ER-phagy: mechanisms, regulation, and diseases connected to the lysosomal clearance of the endoplasmic reticulum DOI Creative Commons
Fulvio Reggiori, Maurizio Molinari

Physiological Reviews, Journal Year: 2022, Volume and Issue: 102(3), P. 1393 - 1448

Published: Feb. 21, 2022

ER-phagy (reticulophagy) defines the degradation of portions endoplasmic reticulum (ER) within lysosomes or vacuoles. It is part self-digestion (i.e., autophagic) programs recycling cytoplasmic material and organelles, which rapidly mobilize metabolites in cells confronted with nutrient shortage. Moreover, selective clearance ER subdomains participates control size activity during stress, reestablishment homeostasis after stress resolution, removal parts aberrant potentially cytotoxic has been segregated. relies on individual and/or concerted activation receptors, peripheral integral membrane proteins that share presence LC3/Atg8-binding motifs their cytosolic domains. involves physical separation from bulk network delivery to endolysosomal/vacuolar catabolic district. This last step accomplished by a variety mechanisms including macro-ER-phagy (in fragments are sequestered double-membrane autophagosomes eventually fuse lysosomes/vacuoles), micro-ER-phagy directly engulfed endosomes/lysosomes/vacuoles), direct fusion ER-derived vesicles lysosomes/vacuoles. dysfunctional specific human diseases, its regulators subverted pathogens, highlighting crucial role for cell organism life.

Language: Английский

Citations

111
Calcium transients on the ER surface trigger liquid-liquid phase separation of FIP200 to specify autophagosome initiation sites DOI Creative Commons

Qiaoxia Zheng,

Yong Chen, Di Chen

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(22), P. 4082 - 4098.e22

Published: Oct. 1, 2022

Highlights•Autophagy induction elicits Ca2+ transients on the outer surface of ER membrane•EPG-4/EI24 controls amplitude, frequency, and duration transients•Ca2+ induce formation fusion-prone, liquid-like FIP200 puncta•ATG9 modulates phase separation organization puncta ERSummaryThe mechanism that initiates autophagosome in multicellular organisms is elusive. Here, we showed autophagy stimuli trigger membrane, whose are controlled by metazoan-specific transmembrane protein EPG-4/EI24. Persistent transients/oscillations cytosolic EI24-depleted cells cause accumulation initiation complexes ER. This defect suppressed attenuating transients. Multi-modal SIM analysis revealed dynamic fusion-prone puncta. Starvation-induced lysosomes also further move to Multiple ER, association depends proteins VAPA/B ATL2/3, assemble into sites. Thus, crucial for triggering specify sites metazoans.Graphical abstract

Language: Английский

Citations

108
Cell death regulation: A new way for natural products to treat osteoporosis DOI Creative Commons
Zhichao Li, Dandan Li, Renchang Chen

et al.

Pharmacological Research, Journal Year: 2022, Volume and Issue: 187, P. 106635 - 106635

Published: Dec. 26, 2022

Osteoporosis is a common metabolic bone disease that results from the imbalance of homeostasis within bone. Intra-bone dependent on precise dynamic balance between resorption by osteoclasts and formation mesenchymal lineage osteoblasts, which comprises series complex highly standardized steps. Programmed cell death (PCD) (e.g., apoptosis, autophagy, ferroptosis, pyroptosis, necroptosis) process involves cascade gene expression events with tight structures. These play certain role in regulating metabolism determining fate cells. Moreover, existing research has suggested natural products derived wide variety dietary components medicinal plants modulate PCDs based different mechanisms, show great potential for prevention treatment osteoporosis, thus revealing emergence more acceptable complementary alternative drugs lower costs, fewer side effects long-term application. Accordingly, this review summarizes types field osteoporosis. perspective targeting PCDs, also discussed roles currently reported osteoporosis involved mechanisms. Based this, provides insights into new molecular mechanisms reference developing anti-osteoporosis future.

Language: Английский

Citations

101