Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10288)
Regulator Name Piezo-type mechanosensitive ion channel component 1 (PIEZO1)
Synonyms
FAM38A, KIAA0233; Membrane protein induced by beta-amyloid treatment; Protein FAM38A
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Gene Name PIEZO1
Gene ID 9780
Regulator Type Protein coding
Uniprot ID Q92508
Sequence
MEPHVLGAVLYWLLLPCALLAACLLRFSGLSLVYLLFLLLLPWFPGPTRCGLQGHTGRLL
RALLGLSLLFLVAHLALQICLHIVPRLDQLLGPSCSRWETLSRHIGVTRLDLKDIPNAIR
LVAPDLGILVVSSVCLGICGRLARNTRQSPHPRELDDDERDVDASPTAGLQEAATLAPTR
RSRLAARFRVTAHWLLVAAGRVLAVTLLALAGIAHPSALSSVYLLLFLALCTWWACHFPI
STRGFSRLCVAVGCFGAGHLICLYCYQMPLAQALLPPAGIWARVLGLKDFVGPTNCSSPH
ALVLNTGLDWPVYASPGVLLLLCYATASLRKLRAYRPSGQRKEAAKGYEARELELAELDQ
WPQERESDQHVVPTAPDTEADNCIVHELTGQSSVLRRPVRPKRAEPREASPLHSLGHLIM
DQSYVCALIAMMVWSITYHSWLTFVLLLWACLIWTVRSRHQLAMLCSPCILLYGMTLCCL
RYVWAMDLRPELPTTLGPVSLRQLGLEHTRYPCLDLGAMLLYTLTFWLLLRQFVKEKLLK
WAESPAALTEVTVADTEPTRTQTLLQSLGELVKGVYAKYWIYVCAGMFIVVSFAGRLVVY
KIVYMFLFLLCLTLFQVYYSLWRKLLKAFWWLVVAYTMLVLIAVYTFQFQDFPAYWRNLT
GFTDEQLGDLGLEQFSVSELFSSILVPGFFLLACILQLHYFHRPFMQLTDMEHVSLPGTR
LPRWAHRQDAVSGTPLLREEQQEHQQQQQEEEEEEEDSRDEGLGVATPHQATQVPEGAAK
WGLVAERLLELAAGFSDVLSRVQVFLRRLLELHVFKLVALYTVWVALKEVSVMNLLLVVL
WAFALPYPRFRPMASCLSTVWTCVIIVCKMLYQLKVVNPQEYSSNCTEPFPNSTNLLPTE
ISQSLLYRGPVDPANWFGVRKGFPNLGYIQNHLQVLLLLVFEAIVYRRQEHYRRQHQLAP
LPAQAVFASGTRQQLDQDLLGCLKYFINFFFYKFGLEICFLMAVNVIGQRMNFLVTLHGC
WLVAILTRRHRQAIARLWPNYCLFLALFLLYQYLLCLGMPPALCIDYPWRWSRAVPMNSA
LIKWLYLPDFFRAPNSTNLISDFLLLLCASQQWQVFSAERTEEWQRMAGVNTDRLEPLRG
EPNPVPNFIHCRSYLDMLKVAVFRYLFWLVLVVVFVTGATRISIFGLGYLLACFYLLLFG
TALLQRDTRARLVLWDCLILYNVTVIISKNMLSLLACVFVEQMQTGFCWVIQLFSLVCTV
KGYYDPKEMMDRDQDCLLPVEEAGIIWDSVCFFFLLLQRRVFLSHYYLHVRADLQATALL
ASRGFALYNAANLKSIDFHRRIEEKSLAQLKRQMERIRAKQEKHRQGRVDRSRPQDTLGP
KDPGLEPGPDSPGGSSPPRRQWWRPWLDHATVIHSGDYFLFESDSEEEEEAVPEDPRPSA
QSAFQLAYQAWVTNAQAVLRRRQQEQEQARQEQAGQLPTGGGPSQEVEPAEGPEEAAAGR
SHVVQRVLSTAQFLWMLGQALVDELTRWLQEFTRHHGTMSDVLRAERYLLTQELLQGGEV
HRGVLDQLYTSQAEATLPGPTEAPNAPSTVSSGLGAEEPLSSMTDDMGSPLSTGYHTRSG
SEEAVTDPGEREAGASLYQGLMRTASELLLDRRLRIPELEEAELFAEGQGRALRLLRAVY
QCVAAHSELLCYFIIILNHMVTASAGSLVLPVLVFLWAMLSIPRPSKRFWMTAIVFTEIA
VVVKYLFQFGFFPWNSHVVLRRYENKPYFPPRILGLEKTDGYIKYDLVQLMALFFHRSQL
LCYGLWDHEEDSPSKEHDKSGEEEQGAEEGPGVPAATTEDHIQVEARVGPTDGTPEPQVE
LRPRDTRRISLRFRRRKKEGPARKGAAAIEAEDREEEEGEEEKEAPTGREKRPSRSGGRV
RAAGRRLQGFCLSLAQGTYRPLRRFFHDILHTKYRAATDVYALMFLADVVDFIIIIFGFW
AFGKHSAATDITSSLSDDQVPEAFLVMLLIQFSTMVVDRALYLRKTVLGKLAFQVALVLA
IHLWMFFILPAVTERMFNQNVVAQLWYFVKCIYFALSAYQIRCGYPTRILGNFLTKKYNH
LNLFLFQGFRLVPFLVELRAVMDWVWTDTTLSLSSWMCVEDIYANIFIIKCSRETEKKYP
QPKGQKKKKIVKYGMGGLIILFLIAIIWFPLLFMSLVRSVVGVVNQPIDVTVTLKLGGYE
PLFTMSAQQPSIIPFTAQAYEELSRQFDPQPLAMQFISQYSPEDIVTAQIEGSSGALWRI
SPPSRAQMKRELYNGTADITLRFTWNFQRDLAKGGTVEYANEKHMLALAPNSTARRQLAS
LLEGTSDQSVVIPNLFPKYIRAPNGPEANPVKQLQPNEEADYLGVRIQLRREQGAGATGF
LEWWVIELQECRTDCNLLPMVIFSDKVSPPSLGFLAGYGIMGLYVSIVLVIGKFVRGFFS
EISHSIMFEELPCVDRILKLCQDIFLVRETRELELEEELYAKLIFLYRSPETMIKWTREK
E

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Family PIEZO family
Function
Pore-forming subunit of a mechanosensitive non-specific cation channel. Generates currents characterized by a linear current-voltage relationship that are sensitive to ruthenium red and gadolinium. Plays a key role in epithelial cell adhesion by maintaining integrin activation through R- Ras recruitment to the ER, most probably in its activated state, and subsequent stimulation of calpain signaling. In the kidney, may contribute to the detection of intraluminal pressure changes and to urine flow sensing. Acts as shear-stress sensor that promotes endothelial cell organization and alignment in the direction of blood flow through calpain activation. Plays a key role in blood vessel formation and vascular structure in both development and adult physiology. Acts as sensor of phosphatidylserine (PS) flipping at the plasma membrane and governs morphogenesis of muscle cells. In myoblasts, flippase-mediated PS enrichment at the inner leaflet of plasma membrane triggers channel activation and Ca2+ influx followed by Rho GTPases signal transduction, leading to assembly of cortical actomyosin fibers and myotube formation.

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HGNC ID
HGNC:28993
KEGG ID hsa:9780
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
PIEZO1 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
Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Degenerative arthritis ICD-11: FA05
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 hCDs (Chondrocytes)
In Vivo Model
Mice were orally administered 0.1 g/kg Co-Q10 daily for 8 weeks after the DMM model was established to investigate the therapeutic effect of Co-Q10 in GPX4-CKO mice with osteoarthritis. Mice and rats were anaesthetized with pentobarbital. Destabilization of the medial meniscus (DMM) surgery was performed under a microscope. The incision was sutured and disinfected daily until it healed.

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Response regulation In mouse osteoarthritis model and chondrocyte experiments, inhibition of Piezo1 channel activity increased GPX4 expression, attenuated ferroptosis phenotype and reduced the severity of osteoarthritis.
Degenerative arthritis [ICD-11: FA05]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Piezo-type mechanosensitive ion channel component 1 (PIEZO1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 hCDs (Chondrocytes)
In Vivo Model
Mice were orally administered 0.1 g/kg Co-Q10 daily for 8 weeks after the DMM model was established to investigate the therapeutic effect of Co-Q10 in GPX4-CKO mice with osteoarthritis. Mice and rats were anaesthetized with pentobarbital. Destabilization of the medial meniscus (DMM) surgery was performed under a microscope. The incision was sutured and disinfected daily until it healed.

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Response regulation In mouse osteoarthritis model and chondrocyte experiments, inhibition of Piezo1 channel activity increased GPX4 expression, attenuated ferroptosis phenotype and reduced the severity of osteoarthritis.
References
Ref 1 Mechanical overloading induces GPX4-regulated chondrocyte ferroptosis in osteoarthritis via Piezo1 channel facilitated calcium influx. J Adv Res. 2022 Nov;41:63-75. doi: 10.1016/j.jare.2022.01.004. Epub 2022 Jan 11.