Acetylation of STX17 (syntaxin 17) controls autophagosome maturation

Shen, Qiuhong; Shi, Yin; Liu, Jiaqi; Su, Hua; Huang, Jingtao; Zhang, Yi; Peng, Chao; Zhou, Tianhua; Sun, Qiming; Wan, Wei; Liu, Wei

doi:10.1080/15548627.2020.1752471

Cited by 83 publications

(75 citation statements)

References 53 publications

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“…Autophagosome maturation, the fusion of autophagosomes and lysosomes, ensures the degradation of autophagic cargoes, which is an essential regulatory step of the autophagy process (Shen et al, 2020). The result met the hypothesis that CQ blocked the fusion between mitophagosomes and lysosomes, causing the reduction of mitochondria‐lysosomes colocalization coincidence (Figure 2b) and further causing the accumulation of mitophagosomes (Figure 3a,b) in vitrified oocytes.…”

Section: Discussionmentioning

confidence: 99%

Mitophagy is involved in the mitochondrial dysfunction of vitrified porcine oocytes

Zhang

et al. 2021

Molecular Reproduction Devel

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Mitochondrial dysfunction is considered a crucial factor aggravating oocyte viability after vitrification‐warming. To clarify the role of mitophagy in mitochondrial extinction of vitrified porcine oocytes, mitochondrial function, ultrastructural characteristics, mitochondria‐lysosomes colocalization, and mitophagic proteins were detected with or without chloroquine (CQ) treatment. The results showed that vitrification caused mitochondrial dysfunction, including increasing reactive oxygen species production, decreasing mitochondrial membrane potential, and mitochondrial DNA copy number. Damaged mitochondrial cristae and mitophagosomes were observed in vitrified oocytes. A highly fused fluorescence distribution of mitochondria and lysosomes was also observed. In the detection of mitophagic flux, mitophagy was demonstrated as increasing fluorescence aggregation of microtubule‐associated protein light chain 3B (LC3B), enhanced colocalization between LC3B, and voltage‐dependent anion channels 1 (VDAC1), and upregulated LC3B‐II/I protein expression ratio. CQ inhibited the degradation of mitophagosomes in vitrified oocytes, manifested as decreased mitochondria‐lysosomes colocalization, increased fluorescence fraction of VDAC1 overlapping LC3B, increased LC3B‐II/I protein expression ratio, and p62 accumulation. The inhibition of mitophagosomes degradation by CQ aggravated mitochondrial dysfunction, including increased oxidative damage, reduced mitochondrial function, and further led to loss of oocyte viability and developmental potentiality. In conclusion, mitophagy is involved in the regulation of mitochondrial function during porcine oocyte vitrification.

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Section: Discussionmentioning

confidence: 99%

Mitophagy is involved in the mitochondrial dysfunction of vitrified porcine oocytes

Zhang

et al. 2021

Molecular Reproduction Devel

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“…CBP is a crucial transcriptional co-activator in the regulation of gene expression via interacting with other transcription factors, such as SATB2, AP-1 and KLF3 [22][23][24]. CBP also acts as a lysine acetyltransferase to regulate protein expressions and functions via direct acetylation e.g., DOT1L, BCAT2, KDM2B and STX17 [14][15][16]25]. Due to the transcription-promoting and LAT activity, CBP is involved in multiple cellular functions and pathological processes especially in tumorigenesis [26][27][28][29][30], but its effect on ovarian cancer has not been fully explored.…”

Section: Discussionmentioning

confidence: 99%

CREBBP knockdown suppressed proliferation and promoted chemo-sensitivity via PERK-mediated unfolded protein response in ovarian cancer

Hu¹,

Yin²,

Ma³

et al. 2021

J. Cancer

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CREBBP, in short CBP, has been reported to be involved in tumorigenesis in various cancers, but its role in ovarian cancer remains largely unexplored. In our study, survival analysis of CBP in patients with ovarian cancer was conducted using the Kaplan-Meier Plotter database, then we utilized specific shRNA targeting CREBBP to block the expression of CBP, and detected its effect on cell proliferation and chemo-sensitivity in ovarian cancer cells. The results showed that high expression of CBP was correlated with poor prognosis in ovarian cancer patients. CREBBP knockdown in ovarian cancer cells significantly inhibited tumor proliferation both in vitro and in vivo . Moreover, CREBBP knockdown promoted chemo-sensitivity in ovarian cancer cells. Mechanism research further demonstrated that CREBBP knockdown attenuated unfolded protein response (UPR), which was mediated by PERK/ATF4/STC2 signaling pathway. Our research linked CBP and UPR in ovarian cancer and may provide new strategies for the clinical treatment of ovarian cancer.

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“…Abnormalities occurring at any stage can influence the pathway function. Previous studies have reported that STX17 binds with two other SNARE proteins, Synaptosomal-associated protein 29 (SNAP29) and VAMP8, to enable the recognition and fusion of autophagosomes and lysosomes (28,29). Thus, when STX17 expression or function is reduced, autophagosome-lysosome fusion is disrupted, resulting in aggregation of lysosomes and autophagosomes and inhibition of the autophagic flux (12).…”

Section: Discussionmentioning

confidence: 99%

Hyperoxia reduces STX17 expression and inhibits the autophagic flux in alveolar type II epithelial cells in newborn rats

et al. 2020

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Supplemental oxygen therapy can be life-saving for premature infants. Our previous study revealed a defect in the autophagic flux in the lung tissues of neonatal rats with hyperoxia-induced bronchopulmonary dysplasia (BPd), but the underlying mechanism remains unknown. Moreover, there are few innovative treatments that can completely alter the course of BPd. The present study examined the expression of Syntaxin 17 (STX17), a protein necessary for autophagosome-lysosome binding, in alveolar type II (AT-II) epithelial cells of neonatal rats with BPD. Neonatal Sprague-Dawley rats were randomly exposed to elevated O 2 levels [fraction of inspired oxygen (FiO 2), 0.8; model group] or normal room air (FiO 2 , 0.21; control group), and the expression levels of STX17, autophagy-related [Microtubule-associated protein 1A/1B-light chain 3B (Lc3B)-II, p62, lysosomal-associated membrane protein 1)] and apoptosis-related (cleaved caspase3) mRNA and proteins were examined in lung tissues. Moreover, the expression levels of the aforementioned proteins were measured in isolated primary AT-II cells cultured in vitro under hyperoxic conditions in the presence or absence of pharmacological modulators of autophagy. Transmission electron microscopy identified that AT-II cell apoptosis and autophagosome aggregation were elevated in the lungs of BPD rats compared with control rats on postnatal day 7. STX17 mRNA and protein expression levels were decreased in lung tissue and isolated AT-II cells as early as postnatal day 3 in BPD rats, while the expression levels of LC3B-II, p62 and cleaved caspase3 were increased, reaching a peak on postnatal day 7. This early reduction in STX17 expression, followed by increased expression in autophagy-and apoptosis-related proteins, was also observed in isolated AT-II cells exposed to hyperoxia in vitro. However, treatment with the autophagy inducers rapamycin or Licl eliminated the hyperoxia-induced reduction in STX17, partially restored the autophagy flux and increased the survival of AT-II cells exposed to hyperoxia. collectively, these results indicated that STX17 expression in AT-II cells was reduced in the early stages of BPD in neonatal rats and may be related to the subsequent hyperoxia-induced block in autophagic flux.

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Acetylation of STX17 (syntaxin 17) controls autophagosome maturation

Cited by 83 publications

References 53 publications

Mitophagy is involved in the mitochondrial dysfunction of vitrified porcine oocytes

Mitophagy is involved in the mitochondrial dysfunction of vitrified porcine oocytes

CREBBP knockdown suppressed proliferation and promoted chemo-sensitivity via PERK-mediated unfolded protein response in ovarian cancer

Hyperoxia reduces STX17 expression and inhibits the autophagic flux in alveolar type II epithelial cells in newborn rats

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