Novel role for theSaccharomyces cerevisiaeoligopeptide transporter Opt2 in drug detoxificationIn memory of Ghassan Belhadj.

Saccharomyces cerevisiae Opt2 is a member of the oligopeptide transporter family that was initially identified to transport tetra- and pentapeptides. Mutants deleted for the OPT2 gene exhibit no growth defects under normal culture conditions. We identified OPT2 from a high-throughput screen that when deleted results in mutants that displayed sensitivity to the anticancer agent bleomycin. The opt2Δ mutant was also reisolated in two additional genome-wide screens designed to identify mutants that are sensitive to the immunosuppressant rapamycin and the divalent metal ion zinc. However, the role of Opt2 in protecting cells against these agents was not investigated. Herein, we show that opt2Δ mutants are also sensitive to a wide variety of toxic agents that are typically detoxified by the vacuoles. Mutants lacking two other related oligopeptide transporters, Opt1 and Ygl114w, showed no significant sensitivities to these drugs, indicating a specific role for Opt2 in drug detoxification. The sensitivities of the opt2Δ mutants were not related to an increased drug uptake but rather to the presence of several small vesicles instead of a functional large vacuole. We propose that Opt2 has a novel function involving the fusion of vesicles to form a mature vacuole.