JOURNAL OF CELL BIOLOGY
·
2023
·Vol. 222
·期 5
·e202201068
·
IF 7.8
Wang Xinyi,Jiang Xiao,Li Boran,Zheng Jiahua,Guo Jiansheng,Gao Lei,Du Mengjie,Weng Xialian,Li Lin,Chen She,Zhang Jingzi,Fang Lei,Liu Ting,Wang Liang,Liu Wei,Neculai Dante,Sun Qiming
Macroautophagy (autophagy) utilizes a serial of receptors to specifically recognize and degrade autophagy cargoes, including damaged organelles, to maintain cellular homeostasis. Upstream signals spatiotemporally regulate the biological functions of selective autophagy receptors through protein post-translational modifications (PTM) such as phosphorylation. However, it is unclear how acetylation directly controls autophagy receptors in selective autophagy. Here, we report that an ER-phagy receptor FAM134B is acetylated by CBP acetyltransferase, eliciting intense ER-phagy. Furthermore, FAM134B acetylation promoted CAMKII-mediated phosphorylation to sustain a mode of milder ER-phagy. Conversely, SIRT7 deacetylated FAM134B to temper its activities in ER-phagy to avoid excessive ER degradation. Together, this work provides further mechanistic insights into how ER-phagy receptor perceives environmental signals for fine-tuning of ER homeostasis and demonstrates how nucleus-derived factors are programmed to control ER stress by modulating ER-phagy.
研究领域:
细胞生物学
·
分子生物学
·
生物化学
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DOI
PubMed
高影响因子
RESEARCH IN MICROBIOLOGY
·
2022
·
IF 3.946
Jiawen Du,He Zhao,Mengsen Zhu,Yixuan Dong,Liping Peng,Jianrong Li,Qiang Zhao,Qilin Yu,Mingchun Li
The unfolded protein response (UPR) is an important pathway to prevent endoplasmic reticulum (ER) stress in eukaryotic cells. In Saccharomyces cerevisiae , Ire1 is a key regulatory factor required for HAC1 gene splicing for further production of functional Hac1 and activation of UPR gene expression. Autophagy is another mechanism involved in the attenuation of ER stress by ER-phagy, and Atg8 is a core protein in autophagy. Both autophagy and UPR are critical for ER stress response, but whether they act individually or in combination in Candida albicans is unknown. In this study, we explored the interaction between Ire1 and the autophagy protein Atg8 for the ER stress response by constructing the atg8 Δ/Δ ire1 Δ/Δ double mutant in the pathogenic fungus C. albicans . Compared to the single mutants atg8 Δ/Δ or ire1 Δ/Δ, atg8 Δ/Δ ire1 Δ/Δ exhibited much higher sensitivity to various ER stress-inducing agents and more severe attenuation of UPR gene expression under ER stress. Further investigations showed that the double mutant had a defect in ER-phagy, which was associated with attenuated vacuolar fusion under ER stress. This study revealed that Ire1 and Atg8 in combination function in the activation of the UPR and ER-phagy to maintain ER homeostasis under ER stress in C. albicans .
研究领域:
分子生物学
·
微生物学
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细胞生物学
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DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 8
·3472
·
IF 4.6
Chao Shi,Yan Wang,Xiangge Tian,Xia Lv,Yue An,Jing Ning,Xiulan Xin,Li Dai,Xiaochi Ma,Lei Feng
Cytochrome P450 1A is one of the vital subfamilies of heme-containing cytochrome P450 enzymes belonging to an important exogenous metabolizing CYP in human. The abnormal of endoplasmic reticulum (ER) may directly affect the functional activity of ER-located CYP1A and be associated with the occurrence and development of various diseases. In the present study, we constructed a selective two-photon fluorescent probeERNMfor rapid and visual detection of endogenous CYP1A that was localized in the ER.ERNMcould target the ER and detect the enzymatically active CYP1A in living cells and tissues. The monitoring ability ofERNMfor the fluctuations in functionality level of CYP1A was confirmed using ER stressed A549 cell. Based on the ER-targeting two-photon probe for CYP1A, the close association of ER state and the functional activity of ER-locating CYP1A was confirmed, which would promote the deep understanding of the biofunction of CYP1A in various ER-related diseases.Keywords:cytochrome P450 1A;fluorescent probe;endoplasmic reticulum-targeting;enzymatically active probe;two-photon
研究领域:
生物化学
·
分子生物学
·
药理学
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DOI
PubMed
高影响因子
Cell Reports
·
2023
·Vol. 42
·期 12
·113480-113480
·
IF 8.8
Liang Y,Meng F,Zhao X,He X,Liu J
The endoplasmic reticulum (ER) is the largest intracellular endomembrane system; it shows dynamic changes upon environmental stress. To maintain ER morphology and homeostasis under stress, the excessive ER membrane and the associated unwanted proteins can be removed via ER-phagy. Although a few ER-phagy receptors have been reported in mammals and yeast, their functional counterparts in plants remain largely unexplored. Here, we report that the HVA22 family protein OsHLP1 is an uncharacterized ER-phagy receptor in rice (Oryza sativa L.). OsHLP1 interacts with OsATG8b and recruits ER subdomains and the cargo protein OsNTL6, a negative immune regulator, to autophagosomes upon infection with the fungus Magnaporthe oryzae, which substantially activates disease resistance in rice. AtHVA22J, an Arabidopsis thaliana OsHLP1 ortholog, induced similar ER-phagy in plants. Altogether, we unraveled a conservative protein family that may act as ER-phagy receptors in higher plants, and in particular, we highlighted their roles in rice immune responses.
研究领域:
植物生物学
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分子生物学
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植物病理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMISTRY
·
2023
·
IF 2.7
Cao Shu-Ya,Liu Yi-Shi,Gao Xiao-Dong,Kinoshita Taroh,Fujita Morihisa
Protein modification by glycosylphosphatidylinositol (GPI) takes place in the endoplasmic reticulum (ER). GPI-anchored proteins (GPI-APs) formed in the ER are transported to the cell surface through the Golgi apparatus. During transport, the GPI-anchor structure is processed. In most cells, an acyl chain modified to the inositol of GPI is removed by a GPI-inositol deacylase, PGAP1, in the ER. Inositol-deacylated GPI-APs become sensitive to bacterial phosphatidylinositol-specific phospholipase C (PI-PLC). We previously reported that GPI-APs are partially resistant to PI-PLC when PGAP1 activity is weakened by the deletion of selenoprotein T (SELT) or cleft lip and palate transmembrane protein 1 (CLPTM1). In this study, we found that the loss of TMEM41B, an ER-localized lipid scramblase, restored PI-PLC sensitivity of GPI-APs in SELT-knockout (KO) and CLPTM1-KO cells. In TMEM41B-KO cells, the transport of GPI-APs as well as transmembrane proteins from the ER to the Golgi was delayed. Furthermore, the turnover of PGAP1, which is mediated by ER-associated degradation, was slowed in TMEM41B-KO cells. Taken together, these findings indicate that inhibition of TMEM41B-dependent lipid scrambling promotes GPI-AP processing in the ER through PGAP1 stabilization and slowed protein trafficking.
研究领域:
细胞生物学
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分子生物学
·
蛋白质运输
·
脂质代谢
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Marine Science
·
2021
·
IF 4.912
Dong Yan-Zou,Xia Tian,Lin Ji-Bin,Wang Ling,Song Kai,Zhang Chun-Xiao
This study aimed to investigate the effects of quercetin (QUE) on fat deposition and the underlying mechanism. Fish were fed four test diets: normal fat diet (NFD), high-fat diet (HFD), and HFD supplemented with 0.5 or 1.0 g/kg quercetin (QUE0.5 or QUE1.0). The results showed that HFD feeding resulted in poor growth and feed utilization while QUE treatment reversed this. The fat contents of serum and liver were increased by HFD and QUE supplementation significantly decreased fat content. Furthermore, gene expressions and ultrastructure observation showed that mitochondrial biogenesis and mitophagy were inhibited and endoplasmic reticulum stress (ERS) in the HFD group. QUE can activate the biogenesis and autophagy of mitochondria and suppress ERS, which is related to its fat-lowering effect.
研究领域:
水产养殖
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营养学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Food & Function
·
2021
·Vol. 12
·期 21
·10741-10749
·
IF 5.396
Yi Zhao,Jia-Gen Cui,Hao Zhang,Xue-Nan Li,Mu-Zi Li,Milton Talukder,Jin-Long Li
Di (2-ethylhexyl) phthalate (DEHP) is a hazardous compound used as a plasticizer in plastic products. As a natural carotenoid, lycopene (LYC) is considered an effective protective agent against various types of organ damage. The present study aimed to investigate the role of mitochondria-endoplasmic reticulum (ER) coupling in LYC preventing DEHP-induced hepatotoxicity. The mice were treated with LYC (5 mg kg−1) and/or DEHP (500 or 1000 mg kg−1). In the present study, LYC prevented DEHP-induced histopathological changes including fibrosis and glycogen storage in the liver. Additionally, LYC alleviated DEHP-induced ultrastructural injury of mitochondria and ER. LYC had the underlying preventability against DEHP-induced mitochondrial dynamics imbalance including an increase in fission and a decrease in fusion. Furthermore, DEHP induced mitochondria-associated endoplasmic reticulum membrane (MAM) disorder-induced ER stress through the ER unfolded protein response (UPRER), but LYC alleviated these alterations. Therefore, LYC prevented DEHP-induced hepatic mitochondrial dynamics and MAM disorder, leading to ER stress. The present study provides novel evidence of mitochondria-ER coupling as a target for LYC that prevents DEHP-induced hepatotoxicity.
研究领域:
毒理学
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药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Man-Sha Wu,Ze-Rui Zhou,Xiao-Yuan Wang,Bin-Bin Chen,Mahmoud Elsayed Hafez,Ji-Fen Shi,Da-Wei Li,Ruo-Can Qian
The endoplasmic reticulum (ER) is crucial for the regulation of multiple cellular processes, such as cellular responses to stress and protein synthesis, folding, and posttranslational modification. Nevertheless, monitoring ER physiological activity remains challenging due to the lack of powerful detection methods. Herein, we built a two-stage cascade recognition process to achieve dynamic visualization of ER stress in living cells based on a fluorescent carbon dot (CD) probe, which is synthesized by a facile one-pot hydrothermal method without additional modification. The fluorescent CD probe enables two-stage cascade ER recognition by first accumulating in the ER as the positively charged and lipophilic surface of the CD probe allows its fast crossing of multiple membrane barriers. Next, the CD probe can specifically anchor on the ER membrane via recognition between boronic acids and o-dihydroxy groups of mannose in the ER lumen. The two-stage cascade recognition process significantly increases the ER affinity of the CD probe, thus allowing the following evaluation of ER stress by tracking autophagy-induced mannose transfer from the ER to the cytoplasm. Thus, the boronic acid-functionalized cationic CD probe represents an attractive tool for targeted ER imaging and dynamic tracking of ER stress in living cells.
研究领域:
细胞生物学
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生物医学工程
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分子生物学
·
成像科学
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产品关联
DOI
PubMed
高影响因子
Nano Today
·
2024
·
IF 13.2
Li Liang,Ning Wang,Xiang Li,Zhuan Zhang,Zhu Zhu,Yan Zhuo,Xiaohe Jiang,Jie Wang,Cong Guo,Shiyan Guo,Pinghong Zhou,Yan Zhu,Yong Gan,Miaorong Yu
Exosomes are nanoscale extracellular vesicles that have become pivotal in advancing targeted drug delivery strategies for cancer therapy. In this study, we conducted a comparative analysis of the intracellular targeting capabilities of differently shaped exosomes, including milk exosome nanorods (MR), ginger exosome nanorods (GR), and cancer cell exosome nanorods (HR), compared to their spherical counterparts. Our observations revealed that exosome nanorods demonstrated effective and sustained targeting of the endoplasmic reticulum (ER) within cancer cells, while exosome nanospheres were captured within lysosomes. Building on this principle, we chose milk-derived exosomes (mExo) for the in vivo research, engineering the surface of MR with folate to enhance their tumor-targeting efficacy. We demonstrated the effective accumulation of these folate-modified MR (FMR) around the ER in cancer cells, as validated in both orthotopic colorectal cancer (CRC) tissues and human CRC biopsy samples. Furthermore, when loaded with curcumin (Cur), the FMR@Cur exhibited remarkable efficacy in suppressing tumors in orthotopic CRC mouse models. This effect is attributed to the targeted delivery of FMR@Cur to the ER, leading to enhanced ER-stress induced apoptosis. Overall, our study underscores the pivotal role of shape engineering in exosome-mediated drug delivery, offering novel insights and paving the way for innovative strategies to enhance the precision of intracellular drug targeting in cancer therapy.
研究领域:
生物医学工程
·
肿瘤学
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药学
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
Autophagy
·
2025
·
IF 14.3
Xue Yang,Linyue Lv,Yuelan Zhang,Zhuyou Zhang,Shaowei Zeng,Xinyi Zhang,Qinyang Wang,Martin Dorf,Shitao Li,Bishi Fu
STING1/MITA not only induces innate immune responses but also triggers macroautophagy/autophagy to selectively degrade signaling molecules. However, the molecular mechanisms regulating STING1-mediated selective autophagy remain unclear. Here, we first report that ATP2A2 directly interacts with STING1, regulating STING1-mediated innate immune response by modulating its polymerization and trafficking, thereby inhibiting DNA virus infection. Notably, while screening for reticulophagy receptors involved in STING1-mediated selective autophagy, we identified SEC62 as an important receptor protein in STING1-mediated reticulophagy. Mechanistically, SEC62 strengthens its interaction with STING1 upon activation and concurrently facilitates STING1-mediated reticulophagy upon starvation, which are dependent on ATP2A2. Furthermore, knocking down SEC62 in WT cells inhibits STING1-mediated MAP1LC3B/LC3B lipidation and autophagosome formation, an effect that is lost in ATP2A2 knockout cells, suggesting that SEC62’s role in STING1-mediated selective autophagy is ATP2A2 dependent. Thus, our findings identify the reticulophagy receptor SEC62 as a novel receptor protein regulating STING1-mediated selective autophagy, providing new insight into the mechanism regarding a reticulophagy receptor in the process of STING1-induced selective autophagy.Abbrevations: aa: amino acids; AP-MS: affinity tag purification-mass spectrometry; ATP2A1: ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1; ATP2A2: ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2; ATP2A3: ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3; CANX: calnexin; CCPG1: cell cycle progression 1; CGAS: cyclic GMP-AMP synthase; ctDNA: calf thymus DNA; dsRNA: double-stranded RNA; diABZI: diamidobenzimidazole; ER: endoplasmic reticulum; ERGIC: ER-Golgi intermediate compartment; EBSS: Earle’s Balanced Salt Solution; EV: empty vector; FL: full length; GOLGA2/GM130: golgin A2; HSV-1: herpes simplex virus type 1; IRF3: interferon regulatory factor 3; IFNs: type I interferons; ISD: interferon stimulatory DNA; KO: knockout; MAVS: mitochondrial antiviral signaling protein; MOI: multiplicity of infection; poly(I:C): polyinosinic-polycytidylic acid; NBR1: NBR1 autophagy cargo receptor; PRR: pattern recognition receptor; reticulophagy: selective autophagic degradation of the ER; RETREG1/FAM134B: reticulophagy regulator 1; RIGI: RNA sensor RIG-I; RTN3L: reticulon 3; SEC62: SEC62 homolog, preprotein translocation factor; SeV: Sendai virus; STIM1: stromal interaction molecule 1; STING1/MITA: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1; TEX264: testis expressed 264, ER-phagy receptor; TMX1: thioredoxin related transmembrane protein 1; VSV: vesicular stomatitis virus; VACV: vaccinia virus; ZMPSTE24: zinc metallopeptidase STE24.
研究领域:
免疫学
·
细胞生物学
·
病毒学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Open Life Sciences
·
2025
·Vol. 20
·期 1
·
IF 1.7
Chengrong Huang,Hao Zhang,Jing Wang,Jianfei Li,Qian Liu,Qiyin Zong,Yunyun Zhang,Qin Wang,Qiang Zhou
A growing body of evidence has shown that hepatitis B surface antigen (HBsAg) mutations can influence the occurrence of occult hepatitis B infection (OBI), particularly amino acid substitutions in small hepatitis B surface proteins (SHBs). The mechanistic basis for these results, however, remains unclear. This study was designed to explore the potential impact and mechanisms of OBI-related SHBs mutations on serum HBsAg. Huh7 and HepG2 cells were transfected with plasmids encoding wild-type (WT) or OBI-related SHB mutation-containing sequences, after which a chemiluminescence approach was used to detect HBsAg levels in cell culture supernatants. Western blotting was further used to assess HBsAg and endoplasmic reticulum stress (ERS)-related protein levels in lysates prepared from these cells, while the localization of HBsAg within cells was assessed via immunofluorescent staining. Cells transfected with OBI-related SHB mutation-encoding plasmids exhibited lower supernatant HBsAg levels than cells transfected with WT plasmids. Intracellular and extracellular HBsAg levels in these mutant plasmid-transfected cells were lower relative to those for WT plasmid-transfected cells, and HBsAg accumulation within the ER was detected via immunofluorescent staining in cells transfected with OBI-related SHB mutation-encoding plasmids, ERS-related protein content was also significantly increased in mutant plasmid-transfected cells as compared to those in the WT group. These results suggest that proteins harboring OBI-related mutations may tend to accumulate in the ER, thereby triggering an ERS response and impairing the transcription and translation of HBsAg via the activation of the unfolded protein response and ER-associated protein degradation pathway. These effects ultimately reduce the overall assembly of HBV virions in the ER and their associated secretion.
研究领域:
病毒学
·
分子生物学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2020
·Vol. 21
·期 17
·6250
·
IF 4.556
Can Si,Jaime A. Teixeira da Silva,Chunmei He,Zhenming Yu,Conghui Zhao,Haobin Wang,Mingze Zhang,Jun Duan
The acetylation or deacetylation of polysaccharides can influence their physical properties and biological activities. One main constituent of the edible medicinal orchid,Dendrobium officinale, is water-soluble polysaccharides (WSPs) with substitutedO-acetyl groups. BothO-acetyl groups and WSPs show a similar trend in different organs, but the genes coding for enzymes that transfer acetyl groups to WSPs have not been identified. In this study, we report that REDUCED WALL ACETYLATION (RWA) proteins may act as acetyltransferases. ThreeDoRWAgenes were identified, cloned, and sequenced. They were sensitive to abscisic acid (ABA), but there were no differences in germination rate and root length between wild type and35S::DoRWA3transgenic lines under ABA stress. Three DoRWA proteins were localized in the endoplasmic reticulum.DoRWA3had relatively stronger transcript levels in organs where acetyl groups accumulated thanDoRWA1andDoRWA2, was co-expressed with polysaccharides synthetic genes, so it was considered as a candidate acetyltransferase gene. The level of acetylation of polysaccharides increased significantly in the seeds, leaves and stems of three35S::DoRWA3transgenic lines compared to wild type plants. These results indicate that DoRWA3 can transfer acetyl groups to polysaccharides and is a candidate protein to improve the biological activity of other edible and medicinal plants.Keywords:acetyl groups;Dendrobium officinale;REDUCED WALL ACETYLATION;endoplasmic reticulum
研究领域:
植物生物化学
·
分子生物学
·
生药学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）