Autophagy and Ciliogenesis

Yamamoto, Yasuhiro; Mizushima, Noboru

doi:10.31662/jmaj.2021-0090

Cited by 24 publications

(12 citation statements)

References 67 publications

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“…The present study then investigated the possible mechanisms responsible for the enhanced autophagy and mitophagy induced by icariin. Previous studies have demonstrated that TFEB regulates the biogenesis of both autophagosomes and lysosomes (Settembre et al, 2011; Yamamoto & Mizushima, 2021). As shown in Figure 3a, the location of the nucleus and cytoskeleton was determined by staining with DAPI and phalloidin; the fluorescence staining of TFEB revealed a significantly higher rate of nucleation in the icariin‐treated cells (Figure 3b).…”

Section: Resultsmentioning

confidence: 98%

“…The process of autophagy is divided into four parts, namely the formation of the phagophore, the formation of autophagosomes, the formation of lysosomes, and the fusion and degradation of the autophagosome–lysosome complex (Yamamoto & Mizushima, 2021). As demonstrated in Figure 4a, icariin notably promoted the expression levels of TFEB/Lamin B1 and LC3II/I in the cells exposed to xo‐LDL.…”

Section: Resultsmentioning

confidence: 99%

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Icariin alleviates ferroptosis‐related atherosclerosis by promoting autophagy in xo‐LDL‐induced vascular endothelial cell injury and atherosclerotic mice

Wang

Meng

Mao

et al. 2023

Phytotherapy Research

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Vascular endothelial cells (VECs) are located between the blood plasma and the vascular tissue, and the ferroptosis (iron‐dependent programmed cell death) of VECs can lead to a range of cardiovascular diseases. Icariin is the main active ingredient of Epimedium brevicornum Maxim., which can improve endothelial cell dysfunction. In the present study, the protective effects of icariin on oxidised low‐density lipoprotein (ox‐LDL)‐treated VECs and high‐fat diet‐fed Apolipoprotein E‐deficient mice were investigated. Inflammatory fibrosis in tissues and inflammatory factors in serum and cell supernatants were detected, and mitochondrial membrane potential and the expression levels of ferroptosis‐associated proteins were also detected. The results revealed that icariin reduced the endothelial atherosclerotic plaque area and collagen fibres in aortic sinus tissue, and increased the viability and mitochondrial membrane potential, whereas it reduced the reactive oxygen species levels of VECs. The nucleation of transcription factor EB (TFEB) and subsequent autophagy were negatively associated with ferroptosis in endothelial cells, and the more prominent the autophagy, the lower the levels of ferroptosis. Furthermore, by co‐treating the cells with icariin and the two autophagy inhibitors, Bafilomycin A1 (blocking autophagosome and lysosome fusion) and 3‐methyladenine (blocking autophagosome formation), respectively, the promoting effects of icariin on autophagy were found to be mediated through the process of autophagosome–lysosome fusion. In in vivo experiments, icariin reduced ferroptosis, alleviated atherosclerotic lesions and increased the rate of TFEB nucleation. Additionally, it was found that ARG304, THR308 and GLN311 were the optimal binding sites for the interaction between icariin and TFEB. Taken together, these results suggest that the fusion of autophagosomes and lysosomes promoted by icarrin enhances autophagy and thus reduces ferroptosis. Therefore, icariin may be a potential candidate for the prevention of ferroptosis of VECs and, thus, for the treatment of cardiovascular diseases.

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Icariin alleviates ferroptosis‐related atherosclerosis by promoting autophagy in xo‐LDL‐induced vascular endothelial cell injury and atherosclerotic mice

Wang

Meng

Mao

et al. 2023

Phytotherapy Research

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“…Because inhibiting ciliogenesis reduces lysosomal protein degradation, impaired autophagy may underlie the obesity phenotype ( Lee et al, 2020 ). When autophagy is disrupted in POMC neurons, axon growth is impaired, and adiposity subsequently develops ( Coupé et al, 2012 )– indicating a bidirectional relationship between ciliogenesis and autophagy regulation ( Yamamoto and Mizushima, 2021 ). High-fat diets, specifically enriched with palmitic acid blunts autophagy by increasing levels of SQSTM1 and reducing the transformation of LC3I-LC3II in POMC neurons.…”

Section: Primary Cilia Integrate Peripheral Signals At Hypothalamic C...mentioning

confidence: 99%

Neuronal primary cilia integrate peripheral signals with metabolic drives

et al. 2023

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Neuronal primary cilia have recently emerged as important contributors to the central regulation of energy homeostasis. As non-motile, microtubule-based organelles, primary cilia serve as signaling antennae for metabolic status. The impairment of ciliary structure or function can produce ciliopathies for which obesity is a hallmark phenotype and global ablation of cilia induces non-syndromic adiposity in mouse models. This organelle is not only a hub for metabolic signaling, but also for catecholamine neuromodulation that shapes neuronal circuitry in response to sensory input. The objective of this review is to highlight current research investigating the mechanisms of primary cilium-regulated metabolic drives for maintaining energy homeostasis.

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“…Autophagy is an intracellular degradation process that plays an important role in maintaining intracellular homeostasis. Ciliogenesis and autophagy share several commons as they both show dual roles in tumorigenesis and could be triggered by nutrient starvation (Yamamoto & Mizushima, 2021). Based on this, recent studies have focused on the crosstalk between these two processes.…”

Section: Primary Cilia Autophagy and Cell Deathmentioning

confidence: 99%

Primary cilia: Structure, dynamics, and roles in cancer cells and tumor microenvironment

Guan

Zhang

et al. 2023

Journal Cellular Physiology

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Despite the initiation of tumor arises from tumorigenic transformation signaling in cancer cells, cancer cell survival, invasion, and metastasis also require a dynamic and reciprocal association with extracellular signaling from tumor microenvironment (TME). Primary cilia are the antenna‐like structure that mediate signaling sensation and transduction in different tissues and cells. Recent studies have started to uncover that the heterogeneous ciliation in cancer cells and cells from the TME in tumor growth impels asymmetric paracellular signaling in the TME, indicating the essential functions of primary cilia in homeostasis maintenance of both cancer cells and the TME. In this review, we discussed recent advances in the structure and assembly of primary cilia, and the role of primary cilia in tumor and TME formation, as well as the therapeutic potentials that target ciliary dynamics and signaling from the cells in different tumors and the TME.

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Autophagy and Ciliogenesis

Cited by 24 publications

References 67 publications

Icariin alleviates ferroptosis‐related atherosclerosis by promoting autophagy in xo‐LDL‐induced vascular endothelial cell injury and atherosclerotic mice

Icariin alleviates ferroptosis‐related atherosclerosis by promoting autophagy in xo‐LDL‐induced vascular endothelial cell injury and atherosclerotic mice

Neuronal primary cilia integrate peripheral signals with metabolic drives

Primary cilia: Structure, dynamics, and roles in cancer cells and tumor microenvironment

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