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During infection, O. tsutsugamushi replicates exclusively in the eukaryotic cytosol near mitochondria and alters host metabolic pathways governed by mitochondria. We report that O. tsutsugamushi induces mitochondrial enzymatic impairment and structural abnormalities without altering mitochondrial abundance or the levels of proteins that maintain mitochondrial homeostasis. Confocal and structured illumination microscopy revealed a selective spatial association between O. tsutsugamushi and the mitochondrial membrane protein, voltage-dependent anion channel (VDAC) but not other mitochondrial proteins. Immunosignal for VDAC paralogs 1 and 3 colocalized with cytosolic O. tsutsugamushi organisms whereas VDAC2 did not. Additionally, the antibody specific for VDAC1 and VDAC3 detected proteins of the expected sizes in Orientia membrane fractions. These findings indicate that O. tsutsugamushi negatively impacts mitochondrial function without overt organelle loss and selectively associates with VDAC1\/VDAC3.<\/jats:p>","DOI":"10.3390\/pathogens15040372","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T16:34:08Z","timestamp":1774974848000},"page":"372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Orientia tsutsugamushi Alters Mitochondrial Function and Selectively Associates with VDAC"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4956-9428","authenticated-orcid":false,"given":"Savannah E.","family":"Sanchez","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, School of Medicine, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1378-9162","authenticated-orcid":false,"given":"Travis J.","family":"Chiarelli","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, School of Medicine, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Billingsley","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, School of Medicine, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6035-7306","authenticated-orcid":false,"given":"Richard T.","family":"Marconi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, School of Medicine, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2778-5066","authenticated-orcid":false,"given":"Jason A.","family":"Carlyon","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, School of Medicine, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"634","DOI":"10.3109\/00365549709035911","article-title":"Scrub Typhus Associated with Multiorgan Failure: A Case Report","volume":"29","author":"Chi","year":"1997","journal-title":"Scand. 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