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Among such natural agents, Chlorella vulgaris (C. vulgaris), a commercially available supplement, is known for its notable heavy metal-binding capacity and ancillary benefits. Yet, the detoxification mechanisms of action of C. vulgaris have remained largely unexplored. In this study, our transcriptomic and signaling analyses demonstrated that the chemically characterized aqueous extract of C. vulgaris may have attenuated Hg2+-induced mitotic catastrophe in HEK-293 cells and was predicted to activate AKT signaling and modulate the expression of zinc finger protein-related genes. Furthermore, in corresponding DMT1-overexpressing cells, the protective effects of the extract were associated with the modulation of translation and ubiquitination pathways. These changes may coincide with the partial recovery of the two major ribosomal stress surveillance pathways. Intriguingly, under conditions in which Hg2+ did not provoke the more severe ribotoxic stress response, the C. vulgaris extract appeared to alleviate Hg2+-induced ribosomal stress by engaging both ribosomal quality control and the integrated stress response, particularly the response of GCN2 to amino acid deficiency. Ultimately, these findings suggest the protective effect of C. vulgaris extract against Hg2+ toxicity is associated with DMT1 at the transcriptome level, warranting further experimental investigation of its potential as a nutraceutical adjuvant in mercury detoxification.<\/jats:p>","DOI":"10.3390\/plants15192896","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:17:54Z","timestamp":1790065074000},"page":"2896","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Protective Effect of Chlorella vulgaris Supplement Against Mercury Exposure Is Associated with DMT1: A Transcriptomic Analysis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1280-7975","authenticated-orcid":false,"given":"Chunmei","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University Mainz, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Sabine M.","family":"Klauck","sequence":"additional","affiliation":[{"name":"Division of Cancer Genome Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT) Heidelberg, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Xiao","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University Mainz, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Dongxiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University Mainz, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Yuanping","family":"Hai","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University Mainz, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2637-1681","authenticated-orcid":false,"given":"Thomas","family":"Efferth","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University Mainz, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1193-2642","authenticated-orcid":false,"given":"Xiaohua","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University Mainz, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"ref_1","unstructured":"Caballero, B. 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