Noncatalytic functions of IPMK are essential for activation of autophagy and liver regeneration

Research output: Contribution to journalComment/debate

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 languageEnglish (US)
JournalAutophagy
DOIs
StatePublished - Jan 1 2019

Keywords

  • AMPK
  • autophagy
  • IPMK (Inositol polyphosphate multikinase)
  • liver
  • ULK

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Noncatalytic functions of IPMK are essential for activation of autophagy and liver regeneration'. Together they form a unique fingerprint.

  • Cite this