Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10215)
Regulator Name Phosphatidate phosphatase LPIN1 (LPIN1)
Synonyms
KIAA0188; Lipin-1
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Gene Name LPIN1
Gene ID 23175
Regulator Type Protein coding
Uniprot ID Q14693
Sequence
MNYVGQLAGQVFVTVKELYKGLNPATLSGCIDIIVIRQPNGNLQCSPFHVRFGKMGVLRS
REKVVDIEINGESVDLHMKLGDNGEAFFVQETDNDQEVIPMHLATSPILSEGASRMECQL
KRGSVDRMRGLDPSTPAQVIAPSETPSSSSVVKKRRKRRRKSQLDSLKRDDNMNTSEDED
MFPIEMSSDEAMELLESSRTLPNDIPPFQDDIPEENLSLAVIYPQSASYPNSDREWSPTP
SPSGSRPSTPKSDSELVSKSTERTGQKNPEMLWLWGELPQAAKSSSPHKMKESSPLSSRK
ICDKSHFQAIHSESSDTFSDQSPTLVGGALLDQNKPQTEMQFVNEEDLETLGAAAPLLPM
IEELKPPSASVVQTANKTDSPSRKRDKRSRHLGADGVYLDDLTDMDPEVAALYFPKNGDP
SGLAKHASDNGARSANQSPQSVGSSGVDSGVESTSDGLRDLPSIAISLCGGLSDHREITK
DAFLEQAVSYQQFVDNPAIIDDPNLVVKIGSKYYNWTTAAPLLLAMQAFQKPLPKATVES
IMRDKMPKKGGRWWFSWRGRNTTIKEESKPEQCLAGKAHSTGEQPPQLSLATRVKHESSS
SDEERAAAKPSNAGHLPLLPNVSYKKTLRLTSEQLKSLKLKNGPNDVVFSVTTQYQGTCR
CEGTIYLWNWDDKVIISDIDGTITRSDTLGHILPTLGKDWTHQGIAKLYHKVSQNGYKFL
YCSARAIGMADMTRGYLHWVNERGTVLPQGPLLLSPSSLFSALHREVIEKKPEKFKVQCL
TDIKNLFFPNTEPFYAAFGNRPADVYSYKQVGVSLNRIFTVNPKGELVQEHAKTNISSYV
RLCEVVDHVFPLLKRSHSSDFPCSDTFSNFTFWREPLPPFENQDIHSASA

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Family Lipin family
Function
Acts as a magnesium-dependent phosphatidate phosphatase enzyme which catalyzes the conversion of phosphatidic acid to diacylglycerol during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis and therefore controls the metabolism of fatty acids at different levels. Is involved in adipocyte differentiation. Acts also as nuclear transcriptional coactivator for PPARGC1A/PPARA regulatory pathway to modulate lipid metabolism gene expression. Recruited at the mitochondrion outer membrane and is involved in mitochondrial fission by converting phosphatidic acid to diacylglycerol.

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HGNC ID
HGNC:13345
KEGG ID hsa:23175
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
LPIN1 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
Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Alcoholic liver disease ICD-11: DB94
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 hLCs (Liver cells)
In Vivo Model
The 7-8-month-old male Lpin1-Tg mice and their age-matched littermate wildtype (WT) controls were divided into four dietary groups: (1) WT control, (2) WT plus ethanol (identical to the control diet but with 5% weight per volume ethanol added), (3) Lpin1-Tg control, and (4) Lpin1-Tg plus ethanol. All mice were fed a Lieber-DeCarli liquid diet (BioServ, Frenchtown, NJ) for 5days. Ethanol groups were then fed Lieber-DeCarli liquid diets containing 5% weight per volume ethanol for 10 days while control mice were pairfed to their ethanol-fed counterparts for 10 days. At day 11, mice in the ethanol groups were gavaged a single dose of ethanol (5 g/kg body weight, 31.25% ethanol), whereas mice in control groups were gavaged an isocaloric dose of dextrin maltose.

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Response regulation LPIN1 overexpression accelerated iron accumulation, caused lipid peroxidation, reduced GSH and GAPDH, and promoted ferroptotic liver damage in mice after ethanol administration. The study sheds light on potential therapeutic approaches for the prevention and treatment of human alcoholic steatohepatitis.
Alcoholic liver disease [ICD-11: DB94]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Phosphatidate phosphatase LPIN1 (LPIN1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 hLCs (Liver cells)
In Vivo Model
The 7-8-month-old male Lpin1-Tg mice and their age-matched littermate wildtype (WT) controls were divided into four dietary groups: (1) WT control, (2) WT plus ethanol (identical to the control diet but with 5% weight per volume ethanol added), (3) Lpin1-Tg control, and (4) Lpin1-Tg plus ethanol. All mice were fed a Lieber-DeCarli liquid diet (BioServ, Frenchtown, NJ) for 5days. Ethanol groups were then fed Lieber-DeCarli liquid diets containing 5% weight per volume ethanol for 10 days while control mice were pairfed to their ethanol-fed counterparts for 10 days. At day 11, mice in the ethanol groups were gavaged a single dose of ethanol (5 g/kg body weight, 31.25% ethanol), whereas mice in control groups were gavaged an isocaloric dose of dextrin maltose.

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Response regulation LPIN1 overexpression accelerated iron accumulation, caused lipid peroxidation, reduced GSH and GAPDH, and promoted ferroptotic liver damage in mice after ethanol administration. The study sheds light on potential therapeutic approaches for the prevention and treatment of human alcoholic steatohepatitis.
References
Ref 1 Adipose-Specific Lipin-1 Overexpression Renders Hepatic Ferroptosis and Exacerbates Alcoholic Steatohepatitis in Mice. Hepatol Commun. 2019 Mar 12;3(5):656-669. doi: 10.1002/hep4.1333. eCollection 2019 May.