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Updated: Oct 19, 2025

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
08:07

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

8.7K

Inositol serves as a natural inhibitor of mitochondrial fission by directly targeting AMPK

Che-Chia Hsu1, Xian Zhang1, Guihua Wang1

  • 1Department of Cancer Biology, Wake Forest Baptist Medical Center, Wake Forest University, Winston-Salem, NC 27101, USA.

Molecular Cell
|September 21, 2021
PubMed

Insights

Inositol restricts mitochondrial fission by inhibiting AMPK activation, independent of its role in phosphoinositides. Declining inositol levels trigger mitochondrial fission, revealing inositol as a key regulator of mitochondrial dynamics.

Area of Science:

  • Cell Biology
  • Metabolism
  • Mitochondrial Biology

Background:

  • Mitochondrial dynamics, governed by fusion and fission, are crucial for cellular function and implicated in human diseases.
  • Alterations in mitochondrial dynamics are linked to various pathological conditions.

Purpose of the Study:

  • To investigate the role of inositol in regulating mitochondrial dynamics, specifically mitochondrial fission.
  • To elucidate the mechanism by which inositol influences AMPK activation and mitochondrial fission.

Main Methods:

  • Investigated the effect of inositol levels on AMPK activation and mitochondrial fission in cellular and mouse models.
  • Utilized IMPA1/2 deficiency to induce inositol decline.
  • Examined the direct binding of inositol to AMPKγ and its competition with AMP.

Main Results:

  • Inositol directly restricts AMPK-dependent mitochondrial fission, independent of its role as a phosphoinositide precursor.
  • Inositol deficiency activates AMPK and promotes mitochondrial fission without altering ATP levels.
  • Inositol accumulation prevents AMPK-dependent mitochondrial fission.
  • Metabolic stress or mitochondrial damage leads to inositol decline and subsequent mitochondrial fission.
  • Inositol binds to AMPKγ, competing with AMP and inhibiting AMPK activation.

Conclusions:

  • The AMP/inositol ratio is a critical determinant for AMPK activation.
  • AMP-activated protein kinase (AMPK) acts as an inositol sensor, with inactivation by inositol restricting mitochondrial fission.
  • This study establishes a novel mechanism where inositol decline is required for AMPK activation and subsequent mitochondrial fission.
Keywords:
AMPAMPKIMPA1energy stressglucose deprivationinosiotl sensorinositolinositol/AMP ratiomitochondrial fissionmitocondrial dynamics

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