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 Ipmk 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.
Original language | English (US) |
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Pages (from-to) | 1473-1474 |
Number of pages | 2 |
Journal | Autophagy |
Volume | 15 |
Issue number | 8 |
DOIs |
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State | Published - Aug 3 2019 |
Keywords
- AMPK
- IPMK (Inositol polyphosphate multikinase)
- ULK
- autophagy
- liver
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology