{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:33:26Z","timestamp":1789140806103,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T00:00:00Z","timestamp":1753488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kidney Foundation of Canada (KFOC) KRESCENT Postdoctoral Award (Salary)","award":["PJT-186237"],"award-info":[{"award-number":["PJT-186237"]}]},{"DOI":"10.13039\/501100000024","name":"KFOC","doi-asserted-by":"publisher","award":["PJT-186237"],"award-info":[{"award-number":["PJT-186237"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Idiopathic childhood nephrotic syndrome is a common glomerulopathy comprising proteinuria, hypoalbuminemia, and edema. Podocyte dysfunction is central to this disease process. Extracellular vesicles are released from stressed cells and can represent a molecular snapshot of the parent cell of origin. We previously showed that urinary large extracellular vesicles (LEVs) derived from podocytes are increased in patients with nephrotic syndrome relapse. Here, we investigated the role of mitochondrial DNA (mtDNA) within LEVs both in vitro and in vivo, revealing the novel finding that podocytes release LEVs containing mtDNA, driven by mitochondrial stress. A puromycin aminonucleoside nephrosis rat model showed foot process effacement on electron microscopy and urinary LEVs with significantly increased mtDNA. Prednisolone, which drives remission in nephrotic syndrome in children, attenuated mitochondrial stress and reduced the amount of mtDNA content within LEVs in vitro. Lastly, urinary LEVs from children with nephrotic syndrome also contain mtDNA, and it is the podocyte LEV-fraction which is preferentially enriched. Overall, these data support a potential mechanism of podocyte mitochondrial stress in non-genetic, idiopathic pediatric nephrotic syndrome.<\/jats:p>","DOI":"10.3390\/ijms26157245","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T10:51:14Z","timestamp":1753699874000},"page":"7245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Extracellular Vesicle Mitochondrial DNA Reflects Podocyte Mitochondrial Stress and Is Associated with Relapse in Nephrotic Syndrome"],"prefix":"10.3390","volume":"26","author":[{"given":"Robert L.","family":"Myette","sequence":"first","affiliation":[{"name":"Division of Pediatric Nephrology, Children\u2019s Hospital of Eastern Ontario Research Institute & Children\u2019s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON K1H 8L1, Canada"},{"name":"Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1N 6N5, Canada"},{"name":"Department of Cellular & Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1N 6N5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chet E.","family":"Holterman","sequence":"additional","affiliation":[{"name":"Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1N 6N5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2446-7783","authenticated-orcid":false,"given":"Mayra","family":"Trentin-Sonoda","sequence":"additional","affiliation":[{"name":"Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1N 6N5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler T.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2032s University, Kingston, ON K7L 3N6, Canada"},{"name":"Department of Biochemistry, The University of Western Ontario, London, ON N6A 3K7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles A.","family":"Lajoie","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, The University of Western Ontario, London, ON N6A 3K7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Cairns","sequence":"additional","affiliation":[{"name":"Interdisciplinary School of Health Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, ON K1N 6N5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Burelle","sequence":"additional","affiliation":[{"name":"Interdisciplinary School of Health Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, ON K1N 6N5, Canada"},{"name":"Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1N 6N5, Canada"},{"name":"Center for Neuromuscular Disease (CNMD), Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nour","family":"El Khatib","sequence":"additional","affiliation":[{"name":"Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1N 6N5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Raman-Nair","sequence":"additional","affiliation":[{"name":"Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1N 6N5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3951-2911","authenticated-orcid":false,"given":"Dylan","family":"Burger","sequence":"additional","affiliation":[{"name":"Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1N 6N5, Canada"},{"name":"Department of Cellular & Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1N 6N5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5241-860X","authenticated-orcid":false,"given":"Christopher R. J.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1N 6N5, Canada"},{"name":"Department of Cellular & Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1N 6N5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0140-6736(18)30536-1","article-title":"Idiopathic nephrotic syndrome in children","volume":"392","author":"Noone","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1152\/ajprenal.00478.2012","article-title":"The podocyte\u2019s response to stress: The enigma of foot process effacement","volume":"304","author":"Kriz","year":"2013","journal-title":"Am. J. Physiol. Ren. 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