AI Article Synopsis
- IPMK (inositol polyphosphate multikinase) is identified as a key regulator of autophagy, functioning independently of its enzyme activity.
- Two main signaling pathways, involving IPMK, AMPK, SIRT1, and ULK1, are crucial for enhancing autophagy-related gene expression and activity.
- The absence of IPMK severely impacts lipophagy, leading to liver damage and hindered regeneration, highlighting its potential as a target for treating autophagy-related diseases.
Article Abstract
Macroautophagy/autophagy plays important roles in health and disease, but mechanisms of its activation are unclear. Recently we established IPMK (inositol polyphosphate multikinase) as a physiological determinant of autophagy independent of its catalytic activity. Two signaling axes, IPMK-AMPK-SIRT1 and IPMK-AMPK-ULK1, appear to mediate the influence of IPMK on autophagy. IPMK enhances autophagy-related transcription by stimulating AMPK-dependent SIRT1 activation, which mediates the deacetylation of histone 4 lysine 16. Furthermore, direct binding of IPMK to ULK and AMPK forms a ternary complex that facilitates AMPK-dependent ULK phosphorylation. Deletion of virtually abolishes lipophagy, promotes liver damage and impairs hepatocyte regeneration. Our study establishes the importance of IPMK in regulation of autophagy and as a drug target for autophagy-related diseases.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613895 | PMC |
| http://dx.doi.org/10.1080/15548627.2019.1615305 | DOI Listing |
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