Glutathione S-transferase ϴ-subunit as a phenotypic suppressor of pmr1Δ strain, the Kluyveromyces lactis model for Hailey-Hailey disease

G. Ficociello, E. Zanni, S. Cialfi, C. Aurizi, G. Biolcati, C. Palleschi, C. Talora, D. Uccelletti

Research output: Contribution to journalArticlepeer-review


Background Hailey–Hailey disease (HHD), also known as familial benign chronic pemphigus, is a rare, chronic and recurrent blistering disorder, histologically characterized by suprabasal acantholysis. HHD has been linked to mutations in ATP2C1, the gene encoding the human adenosine triphosphate (ATP)-powered calcium channel pump. Methods In this work, the genetically tractable yeast Kluyveromyces lactis has been used to study the molecular basis of Hailey-Hailey disease. The K. lactis strain depleted of PMR1, the orthologue of the human ATP2C1 gene, was used to screen a Madin-Darby canine kidney (MDCK) cDNA library to identify genetic interactors able to suppress the oxidative stress occurring in those cells. Results We have identified the Glutathione S-transferase ϴ-subunit (GST), an important detoxifying enzyme, which restores many of the defects associated with the pmr1Δmutant. GST overexpression in those cells suppressed the sensitivity to calcium chelating agents and partially re-established calcium (Ca2 +) homeostasis by decreasing the high cytosolic Ca2 + levels in pmr1Δstrain. Moreover, we found that in the K. lactis mutant the mitochondrial dysfunction was suppressed by GST overexpression independently from calcineurin. In agreement with yeast results, a decreased expression of the human GST counterpart (GSTT1/M1) was observed in lesion-derived keratinocytes from HHD patients. Conclusions These data highlighted the Glutathione S-transferase as a candidate gene associated with Hailey-Hailey disease. General significance Kluyveromyces lactis can be considered a good model to study the molecular basis of this pathology.

Original languageEnglish
Pages (from-to)2650-2657
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Issue number11
Publication statusPublished - Nov 1 2016


  • ATP2C1
  • Calcium
  • Glutathione S-transferase
  • Keratinocytes
  • Oxidative stress
  • PMR1

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Glutathione S-transferase ϴ-subunit as a phenotypic suppressor of pmr1Δ strain, the Kluyveromyces lactis model for Hailey-Hailey disease'. Together they form a unique fingerprint.

Cite this