VAMP8 phosphorylation regulates lysosome dynamics during autophagy DOI Creative Commons
Lei Wang, Jiajie Diao

Autophagy Reports, Journal Year: 2022, Volume and Issue: 1(1), P. 79 - 82

Published: March 31, 2022

In the final critical step for autophagic degradation, lysosomes fuse with autophagosomes to form autolysosomes. Although recent research has suggested that soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins are important lysosome-autophagosome fusion, neither architecture of prefusion state nor regulatory mechanisms have been identified. our study, using structured illumination microscopy, we observed formed clusters around individual autophagosomes, thereby setting stage membrane fusion. Moreover, VAMP8 (vesicle-associated 8) assists in forming these clusters. We also found phosphorylation reduces spontaneous whereas its dephosphorylation promotes fusion events between and both normal autophagy-induced conditions. Our data thus suggest a key role regulation

Language: Английский

VAMP2 controls murine epidermal differentiation and carcinogenesis by regulation of nucleophagy DOI
Han Liu, Peihong Su, Yuanyuan Li

et al.

Developmental Cell, Journal Year: 2024, Volume and Issue: 59(15), P. 2005 - 2016.e4

Published: Aug. 1, 2024

Language: Английский

Citations

4
SNARE proteins: Core engines of membrane fusion in cancer DOI Creative Commons
Hongyi Liu,

Ruiyue Dang,

Wei Zhang

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: unknown, P. 189148 - 189148

Published: July 1, 2024

Language: Английский

Citations

4
Porphyromonas gingivalis, a periodontal pathogen, impairs post-infarcted myocardium by inhibiting autophagosome–lysosome fusion DOI Creative Commons

Yuka Shiheido‐Watanabe,

Yasuhiro Maejima,

Shun Nakagama

et al.

International Journal of Oral Science, Journal Year: 2023, Volume and Issue: 15(1)

Published: Sept. 18, 2023

Abstract While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), underlying mechanisms remain unclear. Autophagy, a cellular quality control process that is activated in diseases, including heart failure, can be suppressed by Porphyromonas gingivalis ( P.g .). However, it uncertain whether autophagy impairment pathogens stimulates development of cardiac dysfunction after MI. Thus, this study aimed to investigate relationship PD MI while focusing on role autophagy. Neonatal rat cardiomyocytes (NRCMs) model mice were inoculated with wild-type . or gingipain-deficient assess effect inhibition Wild-type .-inoculated NRCMs had lower cell viability than those This also revealed gingipains cleave vesicle-associated membrane protein 8 (VAMP8), involved lysosomal sensitive factor attachment receptors (SNAREs), at 47th lysine residue, thereby inhibiting more susceptible rupture, survival rates activity mice. After inoculating genetically modified (VAMP8-K47A) ., they exhibited significantly increased activation compared which rupture enhanced overall rates. These findings suggest gingipains, are virulence factors impair infarcted myocardium cleaving VAMP8 disrupting confirms strong association provides new insights into potential relationship.

Language: Английский

Citations

10
Pivotal roles of Plasmodium falciparum lysophospholipid acyltransferase 1 in cell cycle progression and cytostome internalization DOI Creative Commons

Junpei Fukumoto,

Minako Yoshida,

Suzumi M. Tokuoka

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Jan. 29, 2025

The rapid intraerythrocytic replication of Plasmodium falciparum, a deadly species malaria parasite, requires quick but constant supply phospholipids to support marked cell membrane expansion. In the malarial many enzymes functioning in phospholipid synthesis pathway have not been identified or characterized. Here, we identify P. falciparum lysophospholipid acyltransferase 1 (PfLPLAT1) and show that PfLPLAT1 is vital for asexual parasite cycle progression cytostome internalization. Deficiency results decreased parasitemia prevents transition schizont stage. Parasites lacking also exhibit distinctive omega-shaped vacuoles, indicating disrupted function. Transcriptomic analyses suggest this deficiency impacts DNA regulation. Mass spectrometry-based enzyme assay lipidomic analysis demonstrate recombinant exhibits activity with preference unsaturated fatty acids as its acyl donors lysophosphatidic an acceptor, conditional knockout leading abnormal lipid composition morphological developmental changes including stage arrest. These findings highlight potential target antimalarial therapy, particularly due unique role divergence from human orthologs. has important roles phosphatidic acid essential substance Its dysfunction leads arrest death parasites.

Language: Английский

Citations

0
Pharmacological Advances and Therapeutic Applications of Niclosamide in Cancer and Other Diseases DOI Creative Commons
Umm e Laila, Z Zhao, Dongsheng Xu

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 117527 - 117527

Published: March 1, 2025

Language: Английский

Citations

0
Graphene Oxide Nanosheets Induce Mitochondrial Fragmentation by Cutting through Membrane DOI
Xintian Shao, Zhou Fang,

Miaoling Li

et al.

ACS Materials Letters, Journal Year: 2023, Volume and Issue: 5(9), P. 2308 - 2316

Published: July 29, 2023

Graphene oxide (GO)-based nanomaterials have unique physical, chemical, and biological properties that make their use in biomedical research nanomedicine of enormous interest. However, little is known about sublethal effects on systems, especially mitochondrial damage. Here, by using super-resolution imaging live cells, we discovered GO nanosheets damage membranes a dose-dependent manner both cancer healthy cell lines. Furthermore, observed destroy the integrity cristae. We performed simulations to clarify mechanisms governing behavior found insert into membranes, thereby resulting membrane "cutting" size an essential factor inducing fragmentation. Those results, demonstrating large induce damage, indicate assessment safety profiling GO-based tools products should include careful evaluation mitochondria.

Language: Английский

Citations

9
Mitochondrial nucleoid condensates drive peripheral fission through high membrane curvature DOI Creative Commons
Qixin Chen, Liu‐Yi Liu,

Zhiqi Tian

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(12), P. 113472 - 113472

Published: Nov. 24, 2023

Mitochondria are dynamic organelles that undergo fusion and fission events, in which the mitochondrial membrane DNA (mtDNA) play critical roles. The spatiotemporal organization of mtDNA reflects impacts dynamics. Herein, to study detailed dynamics mtDNA, we rationally develop a dual-color fluorescent probe, mtGLP, could be used for simultaneously monitoring via separate color outputs. By combining mtGLP with structured illumination microscopy monitor dynamics, discover formation nucleoid condensates damaged mitochondria. We further reveal promoted peripheral mitochondria asymmetric segregation. Through simulations, find events occurred when interacted highly curved regions at two ends Overall, show utilize maintain homeostasis.

Language: Английский

Citations

9
Molecular structures and function of the autophagosome-lysosome fusion machinery DOI Creative Commons
Jiajie Diao, Calvin K. Yip, Qing Zhong

et al.

Autophagy Reports, Journal Year: 2024, Volume and Issue: 3(1)

Published: Feb. 4, 2024

Macroautophagy (also known as autophagy) plays a pivotal role in maintaining cellular homeostasis. The terminal step of the multi-step autophagy degradation pathway involves fusion between cargo-laden, double-membraned autophagosome and lytic organelle lysosome/vacuole. Over past decade, various core components molecular machinery that execute this critical event have been identified. This review highlights recent advances understanding structures, biochemical functions, regulatory mechanisms key highly sophisticated including SNARE fusogens, tethering factors, Rab GTPases associated guanine nucleotide exchange other accessory factors.

Language: Английский

Citations

3
Vesicle-associated membrane protein 8 knockdown exerts anti-proliferative, pro-apoptotic, anti-autophagic, and pro-ferroptotic effects on colorectal cancer cells by inhibition of the JAK/STAT3 pathway DOI
Yi Xu, Tianyao Yang,

Qiu Xu

et al.

Journal of Bioenergetics and Biomembranes, Journal Year: 2024, Volume and Issue: 56(4), P. 419 - 431

Published: May 9, 2024

Language: Английский

Citations

3
CENPN suppresses autophagy and increases paclitaxel resistance in nasopharyngeal carcinoma cells by inhibiting the CREB-VAMP8 signaling axis DOI Creative Commons

Bin-Ru Wang,

Ji-Bo Han,

Yang Jiang

et al.

Autophagy, Journal Year: 2023, Volume and Issue: 20(2), P. 329 - 348

Published: Sept. 30, 2023

Chemotherapeutic resistance is one of the most common reasons for poor prognosis patients with nasopharyngeal carcinoma (NPC). We found that CENPN can promote growth, proliferation and apoptosis NPC cells, but its relationship chemotherapeutic in unclear. Here we verified expression level was positively correlated degree paclitaxel (PTX) a through analysis clinical cases. VAMP8 significantly increased after knockdown by transcriptome sequencing. cell experiments inhibited macroautophagy/autophagy PTX resistance. Overexpression reduced inhibitory effects on survival, proliferation, cycle progression cells inhibiting autophagy. In turn, affect phenotype increasing autophagy to achieve sensitization. Sequential reversed PTX-sensitizing effect alone. Experiments nude mice confirmed increase expression, enhance sensitivity PTX. Mechanistic studies showed translocation p-CREB into nucleus resulting decreased binding promoter, thereby transcription VAMP8. These results demonstrate may be marker predicting efficacy potential target inducing chemosensitization agents such as

Language: Английский

Citations

8