TOR inhibitors: from mammalian outcomes to pharmacogenetics in plants and algae

Target of rapamycin (TOR) is a conserved eukaryotic phosphatidylinositol 3-kinase-related kinase that regulates growth and metabolism in response to environment in plants and algae. The study of the plant and algal TOR pathway has largely depended on TOR inhibitors first developed for non-photosynthetic eukaryotes. In animals and yeast, fundamental work on the TOR pathway has benefited from the allosteric TOR inhibitor rapamycin and more recently from ATP-competitive TOR inhibitors (asTORis) that circumvent the limitations of rapamycin. The asTORis, developed for medical application, inhibit TOR complex 1 (TORC1) more efficiently than rapamycin and also inhibit rapamycin-resistant TORCs. This review presents knowledge on TOR inhibitors from the mammalian field and underlines important considerations for plant and algal biologists. It discusses the use of rapamycin and asTORis in plants and algae and concludes with guidelines for physiological studies and genetic screens with TOR inhibitors.