Figure EV2. Model of arsenic metabolism in yeast.

Pentavalent arsenate As(V) enters yeast cells via phosphate transporters (Pho) (Bun‐ya et al, 1996; Yompakdee et al, 1996). The arsenate reductase Acr2 reduces cytosolic As(V) to trivalent arsenite As(III) (Mukhopadhyay & Rosen, 1998; Mukhopadhyay et al, 2000) followed by export by the arsenite permease Acr3 (Wysocki et al, 1997), probably in the form As(OH)₂O⁻, or by import into the vacuole by the ABC transporter Ycf1 as the glutathione conjugate As(GS)₃ (Ghosh et al, 1999). As(III) enters cells through the aquaglyceroporin Fps1 (Wysocki et al, 2001) in the form As(OH)₃ and through hexose permeases (Hxt) (Liu et al, 2004). As(III) can also be extruded via Fps1 down the concentration gradient (Bienert et al, 2008; Maciaszczyk‐Dziubinska et al, 2010). S. cerevisiae increases glutathione (GSH) biosynthesis in response to As(III) exposure for intracellular chelation and protection (Thorsen et al, 2007; Talemi et al, 2014). GSH is also exported via plasma membrane localized ABC transporters (ABC) and specific GSH export proteins (Gex) for extracellular As(III) chelation/detoxification(Thorsen et al, 2012). Acr1 (also called Yap8 or Arr1) is a nuclear transcription factor that senses As(III) and activates transcription of ACR2 and ACR3 (Wysocki et al, 2004). Ask10 (also called Rgc2) is a positive regulator of Fps1 (Beese et al, 2009). For recent overviews of arsenic uptake and detoxification pathways in yeast, see (Wysocki & Tamas, 2010; Wysocki & Tamás, 2011; Talemi et al, 2014).