Akr1 attenuates methylmercury toxicity through the palmitoylation of Meh1 as a subunit of the yeast EGO complex

Zhi Ting Zhang, Yousuke Ogiwara, Yuichi Ito, Akinori Hikida, Nobuhiko Miura, Shusuke Kuge, Akira Naganuma, Gi Wook Hwang

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Background We previously reported that palmitoyltransferase activity of Akr1 is required for alleviation of methylmercury toxicity in yeast. In this study, we identified a factor that alleviates methylmercury toxicity among the substrate proteins palmitoylated by Akr1, and investigated the role of this factor in methylmercury toxicity. Methods Gene disruption and site-directed mutagenesis were used to examine the relationship of methylmercury toxicity and vacuole function. Palmitoylation was investigated using the acyl-biotinyl exchange method. Vacuoles were stained with the fluorescent probe FM4-64. Results We found that Meh1 (alias Ego1), a substrate protein of Akr1, participates in the alleviation of methylmercury toxicity. Moreover, almost no palmitoylation of Meh1 when Akr1 was knocked out, and mutant Meh1, which is not palmitoylated, did not show alleviation of methylmercury toxicity. The palmitoylated Meh1 was involved in the alleviation of methylmercury toxicity as a constituent of EGO complex which suppresses autophagy. Methylmercury caused vacuole deformation, and this was greater in the yeasts knocking out the EGO complex subunits. 3-Methyladenine, an autophagy inhibitor, suppresses vacuole deformation and cytotoxicity caused by methylmercury. The elevated methylmercury sensitivity by Meh1 knockout almost completely disappeared in the presence of 3-methyladenine. Conclusions Akr1 reduces methylmercury toxicity through palmitoylation of Meh1. Furthermore, the EGO complex including Meh1 reduces methylmercury toxicity by suppressing the induction of vacuole deformation caused by methylmercury. General significance These findings propose that Meh1 palmitoylated by Akr1 may act as a constituent of the EGO complex when contributing to the decreased cytotoxicity by negatively controlling the induction of autophagy by methylmercury.

Original languageEnglish
Pages (from-to)1729-1736
Number of pages8
JournalBiochimica et Biophysica Acta - General Subjects
Volume1861
Issue number7
DOIs
Publication statusPublished - 2017 Jul

Keywords

  • Akr1
  • EGO complex
  • Methylmercury
  • Palmitoyltransferase
  • Toxicity
  • Yeast

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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