Accumulation of PtdIns(4)P at the Golgi mediated by reversible oxidation of the PtdIns(4)P phosphatase Sac1 by H2O2

Jung Mi Lim, Sujin Park, Mi Sook Lee, Tamas Balla, Dongmin Kang, Sue Goo Rhee

Research output: Contribution to journalArticlepeer-review

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Phosphatidylinositol 4-phosphate [PtdIns(4)P] plays a key role in the biogenesis of transport vesicles at the Golgi complex by recruiting coat proteins and their accessory factors. The PtdIns(4)P content of the Golgi is determined by the concerted action of PtdIns 4-kinase (PI4K) and PtdIns(4)P phosphatase enzymes. Sac1 (suppressor of actin 1) is the major PtdIns(4)P phosphatase and is localized to the Golgi and endoplasmic reticulum. The targeting of both PI4Ks and Sac1 to the Golgi membrane is extensively regulated, as is the catalytic activity of PI4Ks at the Golgi. However, regulation of the catalytic activity of Sac1 has been largely unexplored. Here we show that Sac1undergoes reversible inactivation in mammalian cells when its catalytic Cys389 residue is oxidized by exogenous H2O2 to form an intramolecular disulfide with Cys392. The oxidative inactivation of Sac1 results in the accumulation of PtdIns(4)P at the Golgi, with this effect also being supported by the H2O2-induced activation of p38 mitogen-activated protein kinase (MAPK), which was previously shown to promote the translocation of Sac1 from the Golgi to the endoplasmic reticulum. The increase in Golgi PtdIns(4)P due to Sac1 inactivation, however, is faster than that due to Sac1 translocation. Exposure of cells to H2O2 also increased membrane protein trafficking from the Golgi to the plasma membrane as well as protein secretion.

Original languageEnglish
Pages (from-to)426-435
Number of pages10
JournalFree Radical Biology and Medicine
StatePublished - Jan 2019

Bibliographical note

Publisher Copyright:
© 2018 Elsevier Inc.


  • Cysteine oxidation
  • Golgi complex
  • Hydrogen peroxide
  • Phosphatidylinositol 4-phosphate
  • Protein trafficking
  • Sac1


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