20.500.12556/DiRROS-29923 Functional genomics screening in Chlamydomonas reinhardtii maps the genetic landscape of tolerance to paraquat and diuron Functional genomics offers a powerful, unbiased approach to elucidating the molecular mechanisms underlying the toxicity of environmental pollutants. In this study, we applied genome-wide screening in Chlamydomonas reinhardtii to investigate two classical herbicides: paraquat and diuron. Our screen successfully uncovered critical nuclear-encoded pathways that govern susceptibility. For both herbicides, we identified genes regulating the assembly and maintenance of the photosynthetic machinery, highlighting the central role of nuclear control over these chloroplast-localized targets. Beyond these target-related factors, we discovered novel nontarget-site resistance mechanisms. For paraquat, we identified intracellular trafficking as the central determinant of toxicity, experimentally characterizing a P5B ATPase transporter and a fatty acid elongation pathway whose disruption, we propose, converges on the same endomembrane delivery route through sphingolipid depletion. In contrast, our screening data suggest that diuron tolerance may be associated with a metabolic strategy focused on energy conservation, where the inactivation of specific NADPH-consuming enzymes could preserve reducing power for essential antioxidant defense. Collectively, these findings demonstrate that functional genomics can reveal novel, complex modes of action even for well-characterized chemicals, providing the mechanistic resolution required to advance modern ecotoxicological risk assessments. paraquat diuron parakvat diuron Chlamydomonas reinhardtii true false true American Chemical Society ZDA Angleški jezik Slovenski jezik © 2026 The Authors. Neznano 2026-06-09 10:31:19 2026-06-09 10:31:20 2026-06-10 03:48:57 0000-00-00 00:00:00 2026 0 0 Nasl. z nasl. zaslona; Soavtorji iz Slovenije: Carissa Bleker, Katja Stare, Tjaša Lukan, Valentina Levak, Magda Tušek Žnidarič, Tina Kosjek, Katarina P van Midden, Marina Klemenčič, Kristina Sepčić, Maruša Kerenčič, Tina Eleršek, Urban Bren, Marko Jukić, Samo Lešnik, Anže Županič; Opis vira z dne 5. 6. 2026; str. A-P iss. Vol. 60 [in press] 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 2025-12-01 2026-05-14 2026-05-27 575.111 1520-5851 10.1021/acs.est.5c17308 280635139 https://pubs.acs.org/doi/10.1021/acs.est.5c17308 1 9af20a27-63dd-11f1-9215-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=45054 RAZ_Godec_Tim_2026.pdf RAZ_Godec_Tim_2026.pdf 1 9DBFAE0ACBF4D7BF363E2E0E43548B84 34ca15ef32eeca4ef427186434120dde3e3b2e2a2c97bf4449e89b0391eeef30 54f51dc3-63de-11f1-9215-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=45055 Institut Jožef Stefan 0 0 0