{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:56:42Z","timestamp":1793228202835,"version":"4.5.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2017,9]]},"abstract":"\n Clinical studies have identified patients with nephrotic syndrome caused by mutations in genes involved in the biosynthesis of coenzyme Q\n 10<\/jats:sub>\n (CoQ\n 10<\/jats:sub>\n ), a lipid component of the mitochondrial electron transport chain and an important antioxidant. However, the cellular mechanisms through which these mutations induce podocyte injury remain obscure. Here, we exploited the striking similarities between\n Drosophila<\/jats:italic>\n nephrocytes and human podocytes to develop a\n Drosophila<\/jats:italic>\n model of these renal diseases, and performed a systematic\n in vivo<\/jats:italic>\n analysis assessing the role of CoQ\n 10<\/jats:sub>\n pathway genes in renal function. Nephrocyte-specific silencing of\n Coq2<\/jats:italic>\n ,\n Coq6<\/jats:italic>\n , and\n Coq8<\/jats:italic>\n , which are genes involved in the CoQ\n 10<\/jats:sub>\n pathway that have been associated with genetic nephrotic syndrome in humans, induced dramatic adverse changes in these cells. In particular, silencing of\n Coq2<\/jats:italic>\n led to an abnormal localization of slit diaphragms, collapse of lacunar channels, and more dysmorphic mitochondria. In addition,\n Coq2<\/jats:italic>\n -deficient nephrocytes showed elevated levels of autophagy and mitophagy, increased levels of reactive oxygen species, and increased sensitivity to oxidative stress. Dietary supplementation with CoQ\n 10<\/jats:sub>\n at least partially rescued these defects. Furthermore, expressing the wild-type human\n COQ2<\/jats:italic>\n gene specifically in nephrocytes rescued the defective protein uptake, but expressing the mutant allele derived from a patient with\n COQ2<\/jats:italic>\n nephropathy did not. We conclude that transgenic\n Drosophila<\/jats:italic>\n lines carrying mutations in the CoQ\n 10<\/jats:sub>\n pathway genes are clinically relevant models with which to explore the pathogenesis of podocyte injury and could serve as a new platform to test novel therapeutic approaches.\n <\/jats:p>","DOI":"10.1681\/asn.2016060626","type":"journal-article","created":{"date-parts":[[2017,4,20]],"date-time":"2017-04-20T20:25:24Z","timestamp":1492719924000},"page":"2607-2617","source":"Crossref","is-referenced-by-count":31,"title":["A Personalized Model of COQ2 Nephropathy Rescued by the Wild-Type COQ2 Allele or Dietary Coenzyme Q10 Supplementation"],"prefix":"10.1681","volume":"28","author":[{"given":"Jun-yi","family":"Zhu","sequence":"first","affiliation":[{"name":"Cancer and Immunology Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"Fu","sequence":"additional","affiliation":[{"name":"Cancer and Immunology Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Richman","sequence":"additional","affiliation":[{"name":"Cancer and Immunology Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanzheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Nephrology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricio E.","family":"Ray","sequence":"additional","affiliation":[{"name":"Genetic Medicine Research, Children\u2019s National Health System, Washington, DC;"},{"name":"Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Han","sequence":"additional","affiliation":[{"name":"Cancer and Immunology Research and"},{"name":"Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2017,4,20]]},"reference":[{"key":"B1-20230819","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1172\/JCI0215094","article-title":"Genetic models: Clues for understanding the pathogenesis of idiopathic nephrotic syndrome.","volume":"109","author":"Antignac","year":"2002","journal-title":"J Clin Invest"},{"key":"B2-20230819","doi-asserted-by":"crossref","first-page":"e907","DOI":"10.1542\/peds.2006-2164","article-title":"Nephrotic syndrome in the first year of life: Two thirds of cases are caused by mutations in 4 genes (NPHS1, NPHS2, WT1, and LAMB2).","volume":"119","author":"Hinkes","year":"2007","journal-title":"Pediatrics"},{"key":"B3-20230819","first-page":"305","article-title":"Renal transplantation in children with congenital nephrotic syndrome: A report of the North American Pediatric Renal Transplant 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