{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:17:39Z","timestamp":1791253059136,"version":"4.1.0"},"reference-count":57,"publisher":"National Academy of Sciences","issue":"37","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,9,11]]},"abstract":"<jats:p>\n                    Parkinson's disease (PD) is a common neurodegenerative movement disorder. Whereas the majority of PD cases are sporadic, rare genetic defects have been linked to this prevalent movement disorder. Mutations in\n                    <jats:italic>DJ-1<\/jats:italic>\n                    are associated with autosomal recessive early-onset PD. The exact biochemical function of DJ-1 has remained elusive. Here we report the generation of\n                    <jats:italic>DJ-1<\/jats:italic>\n                    knockout (KO) mice by targeted deletion of exon 2 and exon 3. There is no observable degeneration of the central dopaminergic pathways, and the mice are anatomically and behaviorally similar to WT mice. Fluorescent Amplex red measurements of H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    indicate that isolated mitochondria from young and old\n                    <jats:italic>DJ-1<\/jats:italic>\n                    KO mice have a 2-fold increase in H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    .\n                    <jats:italic>DJ-1<\/jats:italic>\n                    KO mice of 2\u20133 months of age have a 60% reduction in mitochondrial aconitase activity without compromising other mitochondrial processes. At an early age there are no differences in antioxidant enzymes, but in older mice there is an up-regulation of mitochondrial manganese superoxide dismutase and glutathione peroxidase and a 2-fold increase in mitochondrial glutathione peroxidase activity. Mutational analysis and mass spectrometry reveal that DJ-1 is an atypical peroxiredoxin-like peroxidase that scavenges H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    through oxidation of Cys-106.\n                    <jats:italic>In vivo<\/jats:italic>\n                    there is an increase of DJ-1 oxidized at Cys-106 after 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine intoxication of WT mice. Taken together these data indicate that the\n                    <jats:italic>DJ-1<\/jats:italic>\n                    KO mice have a deficit in scavenging mitochondrial H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    due to the physiological function of DJ-1 as an atypical peroxiredoxin-like peroxidase.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0703219104","type":"journal-article","created":{"date-parts":[[2007,8,31]],"date-time":"2007-08-31T20:54:19Z","timestamp":1188593659000},"page":"14807-14812","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":429,"title":["DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase"],"prefix":"10.1073","volume":"104","author":[{"given":"Eva","family":"Andres-Mateos","sequence":"first","affiliation":[{"name":"*Institute for Cell Engineering,"},{"name":"Department of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine","family":"Perier","sequence":"additional","affiliation":[{"name":"Department of Neurology, Pathology, and Cell Biology, Columbia University, New York, NY 10032; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"*Institute for Cell Engineering,"},{"name":"Department of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Blanchard-Fillion","sequence":"additional","affiliation":[{"name":"Stokes Research Institute and Department of Pharmacology, Children's Hospital of Philadelphia and University of Pennsylvania, 416D Abramson Research Center, 3517 Civic Center Boulevard, Philadelphia, PA 19104-4318"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd M.","family":"Greco","sequence":"additional","affiliation":[{"name":"Stokes Research Institute and Department of Pharmacology, Children's Hospital of Philadelphia and University of Pennsylvania, 416D Abramson Research Center, 3517 Civic Center Boulevard, Philadelphia, PA 19104-4318"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bobby","family":"Thomas","sequence":"additional","affiliation":[{"name":"*Institute for Cell Engineering,"},{"name":"Department of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han Seok","family":"Ko","sequence":"additional","affiliation":[{"name":"*Institute for Cell Engineering,"},{"name":"Department of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Sasaki","sequence":"additional","affiliation":[{"name":"*Institute for Cell Engineering,"},{"name":"Department of Neurology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Ischiropoulos","sequence":"additional","affiliation":[{"name":"Stokes Research Institute and Department of Pharmacology, Children's Hospital of Philadelphia and University of Pennsylvania, 416D Abramson Research Center, 3517 Civic Center Boulevard, Philadelphia, PA 19104-4318"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Przedborski","sequence":"additional","affiliation":[{"name":"Department of Neurology, Pathology, and Cell Biology, Columbia University, New York, NY 10032; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted M.","family":"Dawson","sequence":"additional","affiliation":[{"name":"*Institute for Cell Engineering,"},{"name":"Department of Neurology,"},{"name":"Solomon H. Snyder Department of Neuroscience, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valina L.","family":"Dawson","sequence":"additional","affiliation":[{"name":"*Institute for Cell Engineering,"},{"name":"Department of Neurology,"},{"name":"Solomon H. Snyder Department of Neuroscience, and"},{"name":"Department of Physiology, Johns Hopkins University School of Medicine, 733 North Broadway, Suite 731, Baltimore, MD 21205;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2007,9,11]]},"reference":[{"key":"e_1_3_4_1_2","first-page":"828","volume-title":"Merritt's Neurology","author":"Fahn S","year":"2005","unstructured":"S Fahn, S Przedborski Merritt's Neurology, ed LP Rowland (Lippincott Williams and Wilkins, New York), pp. 828\u2013846 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