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Hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) plays an important role in redox signalling and pathogen-host cell interactions. For monitoring intra- and subcellular redox events, highly sensitive and specific probes are required. Here, we stably expressed the ratiometric H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>redox sensor roGFP2-Orp1 in the cytosol and the mitochondria of<jats:italic>Plasmodium falciparum (P. falciparum)<\/jats:italic>NF54-<jats:italic>attB<\/jats:italic>blood-stage parasites and evaluated its sensitivity towards oxidative stress, selected antimalarial drugs, and novel lead compounds. In both compartments, the sensor showed reproducible sensitivity towards H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>in the low micromolar range and towards antimalarial compounds at pharmacologically relevant concentrations. Upon short-term exposure (4\u2009h), artemisinin derivatives, quinine and mefloquine impacted H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>levels in mitochondria, whereas chloroquine and a glucose-6-phosphate dehydrogenase (G6PD) inhibitor affected the cytosol; 24\u2009h exposure to arylmethylamino steroids and G6PD inhibitors revealed oxidation of mitochondria and cytosol, respectively. Genomic integration of an H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>sensor expressed in subcellular compartments of<jats:italic>P. falciparum<\/jats:italic>provides the basis for studying complex parasite-host cell interactions or drug effects with spatio-temporal resolution while preserving cell integrity, and sets the stage for high-throughput approaches to identify antimalarial agents perturbing redox equilibrium.<\/jats:p>","DOI":"10.1038\/s41598-017-10093-8","type":"journal-article","created":{"date-parts":[[2017,8,30]],"date-time":"2017-08-30T08:58:36Z","timestamp":1504083516000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Hydrogen peroxide dynamics in subcellular compartments of malaria parasites using genetically encoded redox probes"],"prefix":"10.1038","volume":"7","author":[{"given":"Mahsa","family":"Rahbari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Rahlfs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3494-7767","authenticated-orcid":false,"given":"Jude M.","family":"Przyborski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Katharina","family":"Schuh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas H.","family":"Hunt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6753-8938","authenticated-orcid":false,"given":"David A.","family":"Fidock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges E.","family":"Grau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,9,5]]},"reference":[{"key":"10093_CR1","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1111\/nyas.12766","volume":"1342","author":"S Takala-Harrison","year":"2015","unstructured":"Takala-Harrison, S. & Laufer, M. 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