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Comment
. 2022 Jun;32(6):507-508.
doi: 10.1038/s41422-022-00661-7.

PEN2: Metformin's new partner at lysosome

Kei Sakamoto  1 , Niels Jessen  2
Affiliations
Comment

PEN2: Metformin's new partner at lysosome

Kei Sakamoto et al. Cell Res. 2022 Jun.
No abstract available

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Schematic diagram illustrating the regulation of AMPK at lysosomal and non-lysosomal (e.g., cytoplasm, mitochondrion, nucleus) compartments in response to glucose starvation (low glucose) and low or high intracellular concentrations of metformin.
Low glucose availability results in removal of FBP from aldolase leading to the formation of a supercomplex involving the v-ATPase, Ragulator, AXIN, LKB1, and AMPK, thereby triggering phosphorylation/activation of AMPK (via LKB1). Metformin at low concentrations binds to PEN2, and the metformin-bound PEN2 is recruited to v-ATPase via interacting with the transmembrane domain of ATP6AP1, leading to inhibition of v-ATPase and activation of the lysosomal AMPK. Metformin at high concentrations inhibits complex I of the mitochondrial respiratory chain, leading to global AMPK activation through reduced ATP and increased levels of AMP. The illustration is created with BioRender.com.
See this image and copyright information in PMC

Comment on

  • 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. Ma T, et al. Nature. 2022 Mar;603(7899):159-165. doi: 10.1038/s41586-022-04431-8. Epub 2022 Feb 23. Nature. 2022. PMID: 35197629 Free PMC article.

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