General Information of the Ferroptosis Regulator (ID: REG10340)
Regulator Name Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A)
Synonyms
Autophagy-related protein LC3 A; Autophagy-related ubiquitin-like modifier LC3 A; MAP1 light chain 3-like protein 1; MAP1A/MAP1B light chain 3 A; Microtubule-associated protein 1 light chain 3 alpha
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Gene Name MAP1LC3A
Gene ID 84557
Regulator Type Protein coding
Uniprot ID Q9H492
Sequence
MPSDRPFKQRRSFADRCKEVQQIRDQHPSKIPVIIERYKGEKQLPVLDKTKFLVPDHVNM
SELVKIIRRRLQLNPTQAFFLLVNQHSMVSVSTPIADIYEQEKDEDGFLYMVYASQETFG
F

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Family ATG8 family
Function
Ubiquitin-like modifier involved in formation of autophagosomal vacuoles (autophagosomes). While LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation. Through its interaction with the reticulophagy receptor TEX264, participates in the remodeling of subdomains of the endoplasmic reticulum into autophagosomes upon nutrient stress, which then fuse with lysosomes for endoplasmic reticulum turnover.

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HGNC ID
HGNC:6838
KEGG ID hsa:84557
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
MAP1LC3A can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
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Nuclear receptor coactivator 4 (NCOA4) [Driver]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Driver
Responsed Disease Pulmonary fibrosis ICD-11: CB03
Responsed Drug Dihydroquercetin Preclinical
Pathway Response Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
hBEs (Human bronchial epithelial cells)
MRC-5 cells Normal Homo sapiens CVCL_0440
In Vivo Model
Eight-week-old male C57BL/6 mice were purchased from Hubei University of Medicine (Shiyan, China). The SiO2-induced mouse pulmonary fibrosis model was performed. In brief, each group of mice was anesthetized with 1% pentobarbital sodium intraperitoneally at 40 mg/kg body weight and their tracheae had been surgically exposed. In addition, SiO2 suspension (20 mg in 50 ul saline) was instilled in the mice. The vehicle control groups were given an equivalent amount of 0.9% sterile saline. After one week of acclimation, mice were divided randomly into four groups (n = 8 per group). Control group, SiO2 group, SiO2 and low dose of DHQ group (DHQ-L, 10 mg/kg) as well as large dose of DHQ group (DHQ-H, 50 mg/kg).

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Response regulation Dihydroquercetin suppressed ferritinophagy by down-regulation of microtubule-associated protein 1A/ 1B-light chain 3 (LC3), and up-regulation of ferritin heavy chain 1 (FTH1), nuclear receptor co-activator 4 (NCOA4) in activated HBE cells. Research revealed that inhibition of ferritinophagy-mediated HBE cells ferroptosis was responsible for DHQ to ameliorate SiO2-induced lung fibrosis.
Ferritin heavy chain (FTH1) [Suppressor; Marker]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Pulmonary fibrosis ICD-11: CB03
Responsed Drug Dihydroquercetin Preclinical
Pathway Response Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
hBEs (Human bronchial epithelial cells)
MRC-5 cells Normal Homo sapiens CVCL_0440
In Vivo Model
Eight-week-old male C57BL/6 mice were purchased from Hubei University of Medicine (Shiyan, China). The SiO2-induced mouse pulmonary fibrosis model was performed. In brief, each group of mice was anesthetized with 1% pentobarbital sodium intraperitoneally at 40 mg/kg body weight and their tracheae had been surgically exposed. In addition, SiO2 suspension (20 mg in 50 ul saline) was instilled in the mice. The vehicle control groups were given an equivalent amount of 0.9% sterile saline. After one week of acclimation, mice were divided randomly into four groups (n = 8 per group). Control group, SiO2 group, SiO2 and low dose of DHQ group (DHQ-L, 10 mg/kg) as well as large dose of DHQ group (DHQ-H, 50 mg/kg).

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Response regulation Dihydroquercetin suppressed ferritinophagy by down-regulation of microtubule-associated protein 1A/ 1B-light chain 3 (LC3), and up-regulation of ferritin heavy chain 1 (FTH1), nuclear receptor co-activator 4 (NCOA4) in activated HBE cells. Research revealed that inhibition of ferritinophagy-mediated HBE cells ferroptosis was responsible for DHQ to ameliorate SiO2-induced lung fibrosis.
Unspecific Target [Unspecific Target]
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Responsed Disease Liver fibrosis ICD-11: DB93
Responsed Drug Artesunate Investigative
Pathway Response Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
hHSCs (Human hepatic stellate cells)
hHSCs (Human hepatic stellate cells)
In Vivo Model
6-8-week-old, 20 ± 2 g, male ICR mice, obtained from Nanjing Medical University (Nanjing, China), were randomly divided into five groups (n = 8 per group). Mouse model of chronic liver fibrosis was established by 10% carbon tetrachloride (CCl4, 0.5 ml/100 g body weight) injection. Groups are follows: (1) Control group was intraperitoneally (i.p.) injected with olive oil; (2) Model group was i.p. injected with 10% CCl4 every other day a week for 8 weeks; (3) Low-dose artesunate treatment groups were i.p. injected by CCl4 every other day a week for 8 weeks and daily i.p. injected by 50 mg/kg artesunate for last 4 weeks; (4) Middle-dose artesunate treatment groups were i.p. injected by CCl4 every other day a week for 8 weeks and daily i.p. injected by 100 mg/kg artesunate for last 4 weeks; (5) High-dose artesunate treatment groups were i.p. injected by CCl4 every other day a week for 8 weeks and daily i.p. injected by 200 mg/kg artesunate for last 4 weeks.

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Response regulation Artesunate evidently triggered ferritinophagy accompanied by up-regulation of LC3 (microtubule-associated protein light chain 3), Atg3, Atg5, Atg6/beclin1, Atg12 (autophagy related genes) and down-regulation of p62, FTH1 (ferritin heavy chain), NCOA4 (nuclear receptor co-activator 4) in activated HSCs. These results suggested that ferritinophagy-mediated HSC ferroptosis was responsible for artesunate-induced anti-fibrosis efficacy in liver fibrosis.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [3]
Responsed Disease Traumatic brain injury ICD-11: NA07
Responsed Drug Baicalin Terminated
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell autophagy
Cell apoptosis
In Vitro Model
rPNs (Rat primary neurons)
In Vivo Model
Rats were injected with 4 mL/kg of chloral hydrate for anesthesia and then put on a stereotactic apparatus. Subsequently, the needle was tilted at 55 in the sagittal plane and fixed anterior to the bregma (7.5 mm). The needle tip was toward the right and lowered the anterior to the chiasma (2 mm). Finally, the nonheparinized autologous femoral arterial blood (0.3 mL) was injected into a prechiasmatic cistern using a syringe pump. Rat temperature was maintained at 37 ± 0.5 during the surgery. The rats in the sham group were injected with the same dose of saline into a prechiasmatic cistern. At last, rats were monitored for recovery and then returned to cages.

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Response regulation Baicalin was confirmed to suppress the beclin1, LC3-II, and LC3-I protein levels in rat brain tissues. Moreover, we found that baicalin inhibited neuronal apoptosis. Overall, baicalin suppressed autophagy-dependent ferroptosis in early brain injury after subarachnoid hemorrhage.
Pulmonary fibrosis [ICD-11: CB03]
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A) Protein coding
Responsed Drug Dihydroquercetin Preclinical
Pathway Response Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
hBEs (Human bronchial epithelial cells)
MRC-5 cells Normal Homo sapiens CVCL_0440
In Vivo Model
Eight-week-old male C57BL/6 mice were purchased from Hubei University of Medicine (Shiyan, China). The SiO2-induced mouse pulmonary fibrosis model was performed. In brief, each group of mice was anesthetized with 1% pentobarbital sodium intraperitoneally at 40 mg/kg body weight and their tracheae had been surgically exposed. In addition, SiO2 suspension (20 mg in 50 ul saline) was instilled in the mice. The vehicle control groups were given an equivalent amount of 0.9% sterile saline. After one week of acclimation, mice were divided randomly into four groups (n = 8 per group). Control group, SiO2 group, SiO2 and low dose of DHQ group (DHQ-L, 10 mg/kg) as well as large dose of DHQ group (DHQ-H, 50 mg/kg).

    Click to Show/Hide
Response regulation Dihydroquercetin suppressed ferritinophagy by down-regulation of microtubule-associated protein 1A/ 1B-light chain 3 (LC3), and up-regulation of ferritin heavy chain 1 (FTH1), nuclear receptor co-activator 4 (NCOA4) in activated HBE cells. Research revealed that inhibition of ferritinophagy-mediated HBE cells ferroptosis was responsible for DHQ to ameliorate SiO2-induced lung fibrosis.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A) Protein coding
Responsed Drug Dihydroquercetin Preclinical
Pathway Response Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
hBEs (Human bronchial epithelial cells)
MRC-5 cells Normal Homo sapiens CVCL_0440
In Vivo Model
Eight-week-old male C57BL/6 mice were purchased from Hubei University of Medicine (Shiyan, China). The SiO2-induced mouse pulmonary fibrosis model was performed. In brief, each group of mice was anesthetized with 1% pentobarbital sodium intraperitoneally at 40 mg/kg body weight and their tracheae had been surgically exposed. In addition, SiO2 suspension (20 mg in 50 ul saline) was instilled in the mice. The vehicle control groups were given an equivalent amount of 0.9% sterile saline. After one week of acclimation, mice were divided randomly into four groups (n = 8 per group). Control group, SiO2 group, SiO2 and low dose of DHQ group (DHQ-L, 10 mg/kg) as well as large dose of DHQ group (DHQ-H, 50 mg/kg).

    Click to Show/Hide
Response regulation Dihydroquercetin suppressed ferritinophagy by down-regulation of microtubule-associated protein 1A/ 1B-light chain 3 (LC3), and up-regulation of ferritin heavy chain 1 (FTH1), nuclear receptor co-activator 4 (NCOA4) in activated HBE cells. Research revealed that inhibition of ferritinophagy-mediated HBE cells ferroptosis was responsible for DHQ to ameliorate SiO2-induced lung fibrosis.
Liver fibrosis [ICD-11: DB93]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A) Protein coding
Responsed Drug Artesunate Investigative
Pathway Response Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
hHSCs (Human hepatic stellate cells)
hHSCs (Human hepatic stellate cells)
In Vivo Model
6-8-week-old, 20 ± 2 g, male ICR mice, obtained from Nanjing Medical University (Nanjing, China), were randomly divided into five groups (n = 8 per group). Mouse model of chronic liver fibrosis was established by 10% carbon tetrachloride (CCl4, 0.5 ml/100 g body weight) injection. Groups are follows: (1) Control group was intraperitoneally (i.p.) injected with olive oil; (2) Model group was i.p. injected with 10% CCl4 every other day a week for 8 weeks; (3) Low-dose artesunate treatment groups were i.p. injected by CCl4 every other day a week for 8 weeks and daily i.p. injected by 50 mg/kg artesunate for last 4 weeks; (4) Middle-dose artesunate treatment groups were i.p. injected by CCl4 every other day a week for 8 weeks and daily i.p. injected by 100 mg/kg artesunate for last 4 weeks; (5) High-dose artesunate treatment groups were i.p. injected by CCl4 every other day a week for 8 weeks and daily i.p. injected by 200 mg/kg artesunate for last 4 weeks.

    Click to Show/Hide
Response regulation Artesunate evidently triggered ferritinophagy accompanied by up-regulation of LC3 (microtubule-associated protein light chain 3), Atg3, Atg5, Atg6/beclin1, Atg12 (autophagy related genes) and down-regulation of p62, FTH1 (ferritin heavy chain), NCOA4 (nuclear receptor co-activator 4) in activated HSCs. These results suggested that ferritinophagy-mediated HSC ferroptosis was responsible for artesunate-induced anti-fibrosis efficacy in liver fibrosis.
Traumatic brain injury [ICD-11: NA07]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [3]
Target Regulator Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A) Protein coding
Responsed Drug Baicalin Terminated
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell autophagy
Cell apoptosis
In Vitro Model
rPNs (Rat primary neurons)
In Vivo Model
Rats were injected with 4 mL/kg of chloral hydrate for anesthesia and then put on a stereotactic apparatus. Subsequently, the needle was tilted at 55 in the sagittal plane and fixed anterior to the bregma (7.5 mm). The needle tip was toward the right and lowered the anterior to the chiasma (2 mm). Finally, the nonheparinized autologous femoral arterial blood (0.3 mL) was injected into a prechiasmatic cistern using a syringe pump. Rat temperature was maintained at 37 ± 0.5 during the surgery. The rats in the sham group were injected with the same dose of saline into a prechiasmatic cistern. At last, rats were monitored for recovery and then returned to cages.

    Click to Show/Hide
Response regulation Baicalin was confirmed to suppress the beclin1, LC3-II, and LC3-I protein levels in rat brain tissues. Moreover, we found that baicalin inhibited neuronal apoptosis. Overall, baicalin suppressed autophagy-dependent ferroptosis in early brain injury after subarachnoid hemorrhage.
Dihydroquercetin [Preclinical]
In total 2 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Suppressor
Response Target Nuclear receptor coactivator 4 (NCOA4) Driver
Responsed Disease Pulmonary fibrosis ICD-11: CB03
Pathway Response Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
hBEs (Human bronchial epithelial cells)
MRC-5 cells Normal Homo sapiens CVCL_0440
In Vivo Model
Eight-week-old male C57BL/6 mice were purchased from Hubei University of Medicine (Shiyan, China). The SiO2-induced mouse pulmonary fibrosis model was performed. In brief, each group of mice was anesthetized with 1% pentobarbital sodium intraperitoneally at 40 mg/kg body weight and their tracheae had been surgically exposed. In addition, SiO2 suspension (20 mg in 50 ul saline) was instilled in the mice. The vehicle control groups were given an equivalent amount of 0.9% sterile saline. After one week of acclimation, mice were divided randomly into four groups (n = 8 per group). Control group, SiO2 group, SiO2 and low dose of DHQ group (DHQ-L, 10 mg/kg) as well as large dose of DHQ group (DHQ-H, 50 mg/kg).

    Click to Show/Hide
Response regulation Dihydroquercetin suppressed ferritinophagy by down-regulation of microtubule-associated protein 1A/ 1B-light chain 3 (LC3), and up-regulation of ferritin heavy chain 1 (FTH1), nuclear receptor co-activator 4 (NCOA4) in activated HBE cells. Research revealed that inhibition of ferritinophagy-mediated HBE cells ferroptosis was responsible for DHQ to ameliorate SiO2-induced lung fibrosis.
Experiment 2 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Suppressor
Response Target Ferritin heavy chain (FTH1) Suppressor; Marker
Responsed Disease Pulmonary fibrosis ICD-11: CB03
Pathway Response Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
hBEs (Human bronchial epithelial cells)
MRC-5 cells Normal Homo sapiens CVCL_0440
In Vivo Model
Eight-week-old male C57BL/6 mice were purchased from Hubei University of Medicine (Shiyan, China). The SiO2-induced mouse pulmonary fibrosis model was performed. In brief, each group of mice was anesthetized with 1% pentobarbital sodium intraperitoneally at 40 mg/kg body weight and their tracheae had been surgically exposed. In addition, SiO2 suspension (20 mg in 50 ul saline) was instilled in the mice. The vehicle control groups were given an equivalent amount of 0.9% sterile saline. After one week of acclimation, mice were divided randomly into four groups (n = 8 per group). Control group, SiO2 group, SiO2 and low dose of DHQ group (DHQ-L, 10 mg/kg) as well as large dose of DHQ group (DHQ-H, 50 mg/kg).

    Click to Show/Hide
Response regulation Dihydroquercetin suppressed ferritinophagy by down-regulation of microtubule-associated protein 1A/ 1B-light chain 3 (LC3), and up-regulation of ferritin heavy chain 1 (FTH1), nuclear receptor co-activator 4 (NCOA4) in activated HBE cells. Research revealed that inhibition of ferritinophagy-mediated HBE cells ferroptosis was responsible for DHQ to ameliorate SiO2-induced lung fibrosis.
Baicalin [Terminated]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [3]
Drug for Ferroptosis Suppressor
Response Target Unspecific Target
Responsed Disease Traumatic brain injury ICD-11: NA07
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell autophagy
Cell apoptosis
In Vitro Model
rPNs (Rat primary neurons)
In Vivo Model
Rats were injected with 4 mL/kg of chloral hydrate for anesthesia and then put on a stereotactic apparatus. Subsequently, the needle was tilted at 55 in the sagittal plane and fixed anterior to the bregma (7.5 mm). The needle tip was toward the right and lowered the anterior to the chiasma (2 mm). Finally, the nonheparinized autologous femoral arterial blood (0.3 mL) was injected into a prechiasmatic cistern using a syringe pump. Rat temperature was maintained at 37 ± 0.5 during the surgery. The rats in the sham group were injected with the same dose of saline into a prechiasmatic cistern. At last, rats were monitored for recovery and then returned to cages.

    Click to Show/Hide
Response regulation Baicalin was confirmed to suppress the beclin1, LC3-II, and LC3-I protein levels in rat brain tissues. Moreover, we found that baicalin inhibited neuronal apoptosis. Overall, baicalin suppressed autophagy-dependent ferroptosis in early brain injury after subarachnoid hemorrhage.
Artesunate [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [2]
Drug for Ferroptosis Inducer
Response Target Unspecific Target
Responsed Disease Liver fibrosis ICD-11: DB93
Pathway Response Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
hHSCs (Human hepatic stellate cells)
hHSCs (Human hepatic stellate cells)
In Vivo Model
6-8-week-old, 20 ± 2 g, male ICR mice, obtained from Nanjing Medical University (Nanjing, China), were randomly divided into five groups (n = 8 per group). Mouse model of chronic liver fibrosis was established by 10% carbon tetrachloride (CCl4, 0.5 ml/100 g body weight) injection. Groups are follows: (1) Control group was intraperitoneally (i.p.) injected with olive oil; (2) Model group was i.p. injected with 10% CCl4 every other day a week for 8 weeks; (3) Low-dose artesunate treatment groups were i.p. injected by CCl4 every other day a week for 8 weeks and daily i.p. injected by 50 mg/kg artesunate for last 4 weeks; (4) Middle-dose artesunate treatment groups were i.p. injected by CCl4 every other day a week for 8 weeks and daily i.p. injected by 100 mg/kg artesunate for last 4 weeks; (5) High-dose artesunate treatment groups were i.p. injected by CCl4 every other day a week for 8 weeks and daily i.p. injected by 200 mg/kg artesunate for last 4 weeks.

    Click to Show/Hide
Response regulation Artesunate evidently triggered ferritinophagy accompanied by up-regulation of LC3 (microtubule-associated protein light chain 3), Atg3, Atg5, Atg6/beclin1, Atg12 (autophagy related genes) and down-regulation of p62, FTH1 (ferritin heavy chain), NCOA4 (nuclear receptor co-activator 4) in activated HSCs. These results suggested that ferritinophagy-mediated HSC ferroptosis was responsible for artesunate-induced anti-fibrosis efficacy in liver fibrosis.
References
Ref 1 Dihydroquercetin Attenuates Silica-Induced Pulmonary Fibrosis by Inhibiting Ferroptosis Signaling Pathway. Front Pharmacol. 2022 May 12;13:845600. doi: 10.3389/fphar.2022.845600. eCollection 2022.
Ref 2 Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway. Biomed Pharmacother. 2019 Jan;109:2043-2053. doi: 10.1016/j.biopha.2018.11.030. Epub 2018 Nov 26.
Ref 3 Baicalin suppresses autophagy-dependent ferroptosis in early brain injury after subarachnoid hemorrhage. Bioengineered. 2021 Dec;12(1):7794-7804. doi: 10.1080/21655979.2021.1975999.