{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:50:58Z","timestamp":1792792258364,"version":"4.5.0"},"reference-count":25,"publisher":"National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,7,21]]},"abstract":"\n Peroxisomal matrix protein import requires the action of two AAA ATPases, PEX1 and PEX6. Mutations in either the\n PEX1<\/jats:italic>\n or\n PEX6<\/jats:italic>\n gene are the most common cause of the lethal neurologic disorders Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease and account for disease in 80% of all such patients. We report here that overexpression of\n PEX6<\/jats:italic>\n can suppress the phenotypes of certain\n PEX1<\/jats:italic>\n -deficient cells, that overexpression of\n PEX1<\/jats:italic>\n can suppress the phenotypes of certain\n PEX6<\/jats:italic>\n -deficient cells, and that these instances of suppression are allele-specific and require partial activity of the mutated gene. In addition to genetic evidence for interaction between\n PEX1<\/jats:italic>\n and\n PEX6<\/jats:italic>\n , we find that the PEX1 and PEX6 proteins interact in the yeast two-hybrid assay and physically associate with one another\n in vitro<\/jats:italic>\n . We previously identified a missense mutation in\n PEX1<\/jats:italic>\n , G843D, which attenuates\n PEX1<\/jats:italic>\n function and is the most common cause of these diseases, present in one-third of all such patients. The G843D mutation attenuates the interaction between PEX1 and PEX6 in both the two-hybrid system and\n in vitro<\/jats:italic>\n and appears to be suppressed by overexpression of\n PEX6<\/jats:italic>\n . We conclude that PEX1 and PEX6 form a complex of central importance to peroxisome biogenesis and that mutations affecting this complex constitute the most common cause of the Zellweger syndrome spectrum of diseases.\n <\/jats:p>","DOI":"10.1073\/pnas.95.15.8630","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:39:15Z","timestamp":1027679955000},"page":"8630-8635","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":119,"title":["Disruption of a PEX1\u2013PEX6 interaction is the most common cause of the neurologic disorders Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease"],"prefix":"10.1073","volume":"95","author":[{"given":"Brian V.","family":"Geisbrecht","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia S.","family":"Collins","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette E.","family":"Reuber","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Gould","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1998,7,21]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.01.110185.002421"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.09.110193.002305"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.108.5.1657"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1991.tb04889.x"},{"key":"e_1_3_2_5_2","first-page":"2287","volume-title":"Disorders of Peroxisome Biogenesis","author":"Lazarow P B","year":"1995","unstructured":"P B Lazarow, H W Moser Disorders of Peroxisome Biogenesis, eds C Scriver, A Beaudet, W Sly, D Valle (McGraw\u2013Hill, New York), pp. 2287\u20132324 (1995)."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.108.5.1817"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.125.4.755"},{"key":"e_1_3_2_8_2","first-page":"843","volume":"52","author":"Shimozawa N","year":"1993","unstructured":"N Shimozawa, Y Suzuki, T Orii, A Moser, H W Moser, R J A Wanders Am J Hum Genet 52, 843\u2013844 (1993).","journal-title":"Am J Hum Genet"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.135.1.1"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00654.x"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.135.6.1763"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1297-445"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1990.tb08083.x"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0295-115"},{"key":"e_1_3_2_15_2","unstructured":"Dodt G. 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