{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T01:07:12Z","timestamp":1791508032819,"version":"4.3.4"},"reference-count":36,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["K08 5K08AI102989-04"],"award-info":[{"award-number":["K08 5K08AI102989-04"]}]},{"name":"NIH","award":["RWJF 70642"],"award-info":[{"award-number":["RWJF 70642"]}]},{"name":"NIH","award":["60244"],"award-info":[{"award-number":["60244"]}]},{"name":"AMFDP","award":["K08 5K08AI102989-04"],"award-info":[{"award-number":["K08 5K08AI102989-04"]}]},{"name":"AMFDP","award":["RWJF 70642"],"award-info":[{"award-number":["RWJF 70642"]}]},{"name":"AMFDP","award":["60244"],"award-info":[{"award-number":["60244"]}]},{"name":"UCI DOM Chair Research Award","award":["K08 5K08AI102989-04"],"award-info":[{"award-number":["K08 5K08AI102989-04"]}]},{"name":"UCI DOM Chair Research Award","award":["RWJF 70642"],"award-info":[{"award-number":["RWJF 70642"]}]},{"name":"UCI DOM Chair Research Award","award":["60244"],"award-info":[{"award-number":["60244"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Toxoplasma gondii is an Apicomplexan parasite that possesses a well-developed system of scavengers of reactive oxygen species (ROS). Among its components, T. gondii mitochondrial superoxide dismutase (TgSOD2) is essential, as predicted by the CRISPR phenotype index and evidenced by the non-viability of its constitutive knockouts. As an obligate intracellular parasite, TgSOD2 is upregulated during extracellular stages. Herein, we generated a viable TgSOD2 knockdown mutant using an inducible auxin\u2013degron system to explore the biological role of TgSOD2 in T. gondii. Depletion of TgSOD2 led to impaired parasite growth and replication, reduced mitochondrial membrane potential (MMP), abnormalities in the distribution of ATP synthase within its mitochondrial electron transport chain (mETC), and increased susceptibility to mETC inhibitors. Through a proximal biotinylation approach, we identified the interactions of TgSOD2 with complexes IV and V of its mETC, suggesting that these sites are sensitive to ROS. Our study provides the first insights into the role of TgSOD2 in maintaining its mitochondrial redox homeostasis and subsequent parasite replication fitness. Significance:\u00a0Toxoplasma gondii infects nearly a third of the world population and can cause fetal miscarriages or life-threatening complications in vulnerable patients. Current therapies do not eradicate the parasite from the human hosts, rendering them at risk of recurrence during their lifetimes. T. gondii has a single mitochondrion, which is well-known for its susceptibility to oxidative damage that leads to T. gondii\u2019s death. Therefore, targeting T. gondii mitochondrion remains an attractive therapeutic strategy for drug development. T. gondii\u2019s mitochondrial superoxide dismutase is an antioxidant protein in the parasite mitochondrion and is essential for its survival. Understanding its biological role could reveal mitochondrial vulnerabilities in T. gondii and provide new leads for the development of effective treatments for T. gondii infections.<\/jats:p>","DOI":"10.3390\/biom15070972","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T11:19:27Z","timestamp":1751887167000},"page":"972","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Elucidating the Role of Toxoplasma gondii\u2019s Mitochondrial Superoxide Dismutase"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0262-0617","authenticated-orcid":false,"given":"James Alexander","family":"Tirtorahardjo","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0445-4196","authenticated-orcid":false,"given":"Christopher I-H.","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Areej","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8802-1118","authenticated-orcid":false,"given":"Rosa M.","family":"Andrade","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, University of California Irvine, Irvine, CA 92697, USA"},{"name":"Department of Microbiology and Molecular Genetics, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3848","DOI":"10.4103\/jfmpc.jfmpc_753_20","article-title":"Seroprevalence of Toxoplasma gondii infection: An umbrella review of updated systematic reviews and meta-analyses","volume":"9","author":"Rahmanian","year":"2020","journal-title":"J. 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