Abstract
Selenium is a micronutrient in most eukaryotes, including humans, which is well known for having an extremely thin border between beneficial and toxic concentrations. Soluble tetravalent selenite is the predominant environmental form and also the form that is applied in the treatment of human diseases. To acquire this nutrient from low environmental concentrations as well as to avoid toxicity, a well-controlled transport system is required. Here we report that Jen1p, a proton-coupled monocarboxylate transporter in S. cerevisiae, catalyzes high-affinity uptake of selenite. Disruption of JEN1 resulted in selenite resistance, and overexpression resulted in selenite hypersensitivity. Transport assay showed that overexpression of Jen1p enables selenite accumulation in yeast compared with a JEN1 knock out strain, indicating the Jen1p transporter facilitates selenite accumulation inside cells. Selenite uptake by Jen1p had a Km of 0.91 mM, which is comparable to the Km for lactate. Jen1p transported selenite in a proton-dependent manner which resembles the transport mechanism for lactate. In addition, selenite and lactate can inhibit the transport of each other competitively. Therefore, we postulate selenite is a molecular mimic of monocarboxylates which allows selenite to be transported by Jen1p.
Highlights
Selenium was once believed to be purely a toxin until the requirement was observed in mammals (Stadtman, 2002)
Selenite tolerance of a wild-type (WT) strain, BY4741 (OpenBiosystem), QZ1 (JEN1⌬), QZ1 bearing vector plasmid pDR196 (QZ1pDR196) and QZ1 bearing plasmid pJEN1 (QZ1pJEN1), were assayed for selenite tolerance growing in minimal SD medium with either 2% galactose or glucose medium as carbon source
WT cells grown with glucose as a carbon source exhibited resistance to selenite that was comparable to the tolerance of QZ1 (Figure 1B)
Summary
Selenium was once believed to be purely a toxin until the requirement was observed in mammals (Stadtman, 2002). Some low-molecular-weight selenium compounds have been shown to be responsible for clinical benefits of selenium (Davis and Uthus, 2003) These nonprotein selenium compounds, such as methylselenocysteine (Vadhanavikit et al, 1993) and inorganic selenite, have diverse roles, including scavenging radicals (Yamashita and Yamashita, 2010), attenuating heavy metal toxicity (Heath et al, 2010), serving as an anaerobic electron acceptor (Kabiri et al, 2009), preventing mutation of DNA (Seo et al, 2002), affecting signal transduction (Park et al, 2000a; Park et al, 2000b), maintaining metal homeostasis (Blessing et al, 2004), and other not fully characterized functions. Some eukaryotes, such as S. cerevisiae, have lost their selenoprotein biosynthetic machinery while retaining utilization of sele-
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