Involvement of Thioredoxin Peroxidase Type II (Ahp1p) of Saccharomyces cerevisiae in Mn²⁺ Homeostasis

Abstract

To identify new proteins involved in Mn²⁺ homeostasis, we isolated Mn²⁺-resistant mutants of Saccharomyces cerevisiae starting from a calcineurin-deficient, Mn²⁺ hypersensitive strain (Δcmp1 Δcmp2). The mutations were found to lie in the PMR1 gene, known to encode a “P-type” Ca²⁺-ATPase that transports Ca²⁺ and Mn²⁺ from the cytosol to the Golgi apparatus. A second gene, AHP1, was cloned as a suppressor of the Mn²⁺ tolerance of a Δcmp1 Δcmp2 pmr1 mutant. Ahp1p was recently described as a thioredoxin peroxidase type II, an antioxidant protein with alkyl hydroperoxide defense properties in yeast. AHP1 disruption in strain W303 decreased tolerance to Mn²⁺ and H₂O₂. We found that a GFP-Ahp1p fusion construct was in the cytosol when cells were grown in glucose, and in the mitochondria when cells were grown in oleate. Based on Mn²⁺ transport data, we concluded that Ahp1p is involved in cellular Mn²⁺ homeostasis in trafficking of Mn²⁺ from cytosol to mitochondria and from cytosol for export across the plasma membrane.

• AHP1
• manganese
• organellar trafficking
• Saccharomyces cerevisiae