title: Whi2 enhances methylmercury toxicity in yeast via inhibition of Akr1 palmitoyltransferase activity.
abstract: BACKGROUND
  We have previously reported that Whi2 enhances the toxicity of methylmercury in yeast. In the present study we examined the proteins known to interact with Whi2 to find those that influence the toxicity of methylmercury.
  
  
  METHODS
  Gene disruption and site-directed mutagenesis were employed to examine the relationship of mercury toxicity and palmitoylation. Protein palmitoylation was examined using the acyl-biotinyl exchange method. Protein-protein interactions were detected by immunoprecipitation and immunoblotting.
  
  
  RESULTS
  We found that deletion of Akr1, a palmitoyltransferase, rendered yeast cells highly sensitive to methylmercury, and Akr1 is necessary for the methylmercury resistance of Whi2-deleted yeast. Palmitoyltransferase activity of Akr1 has an important role in the alleviation of methylmercury toxicity. Whi2 deletion or methylmercury treatment enhanced the palmitoyltransferase activity of Akr1, and methylmercury treatment reduced the binding between Akr1 and Whi2.
  
  
  CONCLUSIONS
  Whi2 bonds to Akr1 (a protein that is able to alleviate methylmercury toxicity) and thus inhibits Akr1's palmitoyltransferase activity, which leads to enhanced methylmercury toxicity. In contrast, methylmercury might break the bond between Whi2 and Akr1, which enhances the palmitoyltransferase activity of Akr1 to alleviate methylmercury toxicity.
  
  
  CONCLUSIONS
  This study's findings propose that the Whi2/Akr1 system can be regarded as a defense mechanism that detects methylmercury incorporation of yeast cells and alleviates its toxicity.
authors.affiliation: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan. Electronic address: gwhwang@m.tohoku.ac.jp.
authors.forename: Gi-Wook
authors.initials: GW
authors.lastname: Hwang
authors.affiliation: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Fukumitsu
authors.affiliation: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Ogiwara
authors.affiliation: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan; School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0232, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Division of Health Effects Research, Japan National Institute of Occupational Safety and Health, 6-21-1 Nagao, Tama-ku, Kawasaki 214-8585, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Miura
authors.affiliation: Department of Microbiology, Tohoku Pharmaceutical University, Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Kuge
authors.affiliation: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Naganuma
mesh_terms: D000217:Acyltransferases / Q000037:antagonists & inhibitors* / Q000502:physiology; D008767:Methylmercury Compounds / Q000633:toxicity*; D012441:Saccharomyces cerevisiae / Q000187:drug effects*; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology*
chemical_list: D008767:Methylmercury Compounds; D029701:Saccharomyces cerevisiae Proteins; C470937:Whi2 protein, S cerevisiae; D000217:Acyltransferases; C107846:AKR1 protein, S cerevisiae
keywords: Akr1; Methylmercury; Palmitoyltransferase; Whi2; Yeast