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Low-dose metformin targets the lysosomal AMPK pathway through PEN2.

Ma T, Tian X, Zhang B, Li M, Wang Y, Yang C, Wu J, Wei X, Qu Q, Yu Y, Long S, Feng JW, Li C, Zhang C, Xie C, Wu Y, Xu Z, Chen J, Yu Y, Huang X, He Y, Yao L, Zhang L, Zhu M, Wang W, Wang ZC, Zhang M, Bao Y, Jia W, Lin SY, Ye Z, Piao HL, Deng X, Zhang CS, Lin SC
Nature. 2022 Mar;603(7899):159-165. doi: 10.1038/s41586-022-04431-8. Epub 2022 Feb 23. (Link opens in a new window) PubMed (Link opens in a new window) Article

Plasmids from Article

ID Plasmid Purpose
183639pBoBi-hPEN2 20ALentiviral expression of a PEN2 mutant showing impaired affinity with ATP6AP1.
183640pBoBi-hPEN2 2ALentiviral expression of a PEN2 mutant losing its binding affinity to metformin at the N-terminus (cytosolic face).
183641pBoBi-hPEN2 D90ALentiviral expression of a PEN2 mutant losing its binding affinity to metformin at the C-terminus (lysosome lumen).
183642pBoBi-hAP1 Δ420-440To (stably) express a mutant of ATP6AP1 lacking the interacting domain with PEN2; lentiviral expression
183643pcDNA3.3-hAP1 420-440To (ectopically) express a mutant of ATP6AP1 lacking the interacting domain with PEN2; mammalian expression
183644pcDNA3.3-hAP1 1-419To (ectopically) express a mutant of ATP6AP1 lacking the interacting domain with PEN2; mammalian expression
183645pBoBi-hAP1-C-LAMP2 TMLentiviral expression of a mutant of ATP6AP1 with its PEN2-interacting domain replaced with the transmembrane (TM) domain of LAMP2.
183646pBoBi-hLAMP2-C-PEN2Lentiviral expression of a lysosome-residential PEN2.
183647pBoBi-hTOMM20-C-PEN2Lentiviral expression of a mitochondrion-residential PEN2.
183648pBoBi-hSEC61B-C-PEN2Lentiviral expression of a ER-residential PEN2.
183649pBoBi-hGOLGA2-C-PEN2Lentiviral expression of a golgi-residential PEN2.

Antibodies from Article