PEX6

From yeast to plants to humans, there is only one verified function of PEX6; PEX6 (and PEX1) removes PEX5 from the peroxisomal membrane so that PEX5 may do additional rounds of peroxisomal import. Human PEX6 can genetically complement plant pex6 mutants, which highlights functional conservation.{{cite journal | vauthors = Zolman BK, Bartel B | title = An Arabidopsis indole-3-butyric acid-response mutant defective in PEROXIN6, an apparent ATPase implicated in peroxisomal function | language = en | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 6 | pages = 1786–91 | date = February 2004 | pmid = 14745029 | doi = 10.1073/pnas.0304368101 | pmc=341854| bibcode = 2004PNAS..101.1786Z | doi-access = free }} Work with pex6 mutants in Arabidopsis thaliana has shown that PEX6 may have a role in consuming oil body (plant-specific lipid droplets).{{cite journal | vauthors = Gonzalez KL, Fleming WA, Kao YT, Wright ZJ, Venkova SV, Ventura MJ, Bartel B | title = Disparate peroxisome-related defects in Arabidopsis pex6 and pex26 mutants link peroxisomal retrotranslocation and oil body utilization | language = en | journal = The Plant Journal | volume = 92 | issue = 1 | pages = 110–128 | date = October 2017 | pmid = 28742939 | doi = 10.1111/tpj.13641 | pmc=5605450}} Work with yeast pex6 mutants has shown that PEX6 is a key player in the autophagy of peroxisomes called pexophagy.{{cite journal | vauthors = Nuttall JM, Motley AM, Hettema EH | title = Deficiency of the exportomer components Pex1, Pex6, and Pex15 causes enhanced pexophagy in Saccharomyces cerevisiae | journal = Autophagy | volume = 10 | issue = 5 | pages = 835–45 | date = May 2014 | pmid = 24657987 | doi = 10.4161/auto.28259 | pmc=5119063}}

Mutations in the genes encoding PEX6, along with PEX1, are the leading causes of peroxisomal biogenesis disorders,{{cite journal | vauthors = Waterham HR, Ebberink MS | title = Genetics and molecular basis of human peroxisome biogenesis disorders | journal = Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | volume = 1822 | issue = 9 | pages = 1430–41 | date = September 2012 | pmid = 22871920 | doi = 10.1016/j.bbadis.2012.04.006 | doi-access = free }} such as Zellweger Syndrome spectrum, infantile Refsum disease, and neonatal adrenoleukodystrophy. These genetic diseases are autosomal recessive and occur in 1 of every 50,000 births.{{cite journal | vauthors = Braverman NE, Raymond GV, Rizzo WB, Moser AB, Wilkinson ME, Stone EM, Steinberg SJ, Wangler MF, Rush ET, Hacia JG, Bose M | title = Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines | journal = Molecular Genetics and Metabolism | volume = 117 | issue = 3 | pages = 313–21 | date = March 2016 | pmid = 26750748 | doi = 10.1016/j.ymgme.2015.12.009 | pmc=5214431}} Because of the autosomal recessive inheritance of Zellweger Syndrome, PEX6 can usually be found in larger carrier screening gene panels.

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• {{cite journal | vauthors = Matsumoto N, Tamura S, Moser A, Moser HW, Braverman N, Suzuki Y, Shimozawa N, Kondo N, Fujiki Y | title = The peroxin Pex6p gene is impaired in peroxisomal biogenesis disorders of complementation group 6 | journal = Journal of Human Genetics | volume = 46 | issue = 5 | pages = 273–7 | year = 2001 | pmid = 11355018 | doi = 10.1007/s100380170078 | doi-access = free }}
• {{cite journal | vauthors = Tamura S, Matsumoto N, Imamura A, Shimozawa N, Suzuki Y, Kondo N, Fujiki Y | title = Phenotype-genotype relationships in peroxisome biogenesis disorders of PEX1-defective complementation group 1 are defined by Pex1p-Pex6p interaction | journal = The Biochemical Journal | volume = 357 | issue = Pt 2 | pages = 417–26 | date = July 2001 | pmid = 11439091 | pmc = 1221968 | doi = 10.1042/0264-6021:3570417 }}
• {{cite journal | vauthors = Raas-Rothschild A, Wanders RJ, Mooijer PA, Gootjes J, Waterham HR, Gutman A, Suzuki Y, Shimozawa N, Kondo N, Eshel G, Espeel M, Roels F, Korman SH | title = A PEX6-defective peroxisomal biogenesis disorder with severe phenotype in an infant, versus mild phenotype resembling Usher syndrome in the affected parents | journal = American Journal of Human Genetics | volume = 70 | issue = 4 | pages = 1062–8 | date = April 2002 | pmid = 11873320 | pmc = 379104 | doi = 10.1086/339766 }}
• {{cite journal | vauthors = Matsumoto N, Tamura S, Fujiki Y | title = The pathogenic peroxin Pex26p recruits the Pex1p-Pex6p AAA ATPase complexes to peroxisomes | journal = Nature Cell Biology | volume = 5 | issue = 5 | pages = 454–60 | date = May 2003 | pmid = 12717447 | doi = 10.1038/ncb982 | s2cid = 2426040 }}
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• {{cite journal | vauthors = Furuki S, Tamura S, Matsumoto N, Miyata N, Moser A, Moser HW, Fujiki Y | title = Mutations in the peroxin Pex26p responsible for peroxisome biogenesis disorders of complementation group 8 impair its stability, peroxisomal localization, and interaction with the Pex1p x Pex6p complex | journal = The Journal of Biological Chemistry | volume = 281 | issue = 3 | pages = 1317–23 | date = January 2006 | pmid = 16257970 | doi = 10.1074/jbc.M510044200 | doi-access = free }}
• {{cite journal | vauthors = Tamura S, Yasutake S, Matsumoto N, Fujiki Y | title = Dynamic and functional assembly of the AAA peroxins, Pex1p and Pex6p, and their membrane receptor Pex26p | journal = The Journal of Biological Chemistry | volume = 281 | issue = 38 | pages = 27693–704 | date = September 2006 | pmid = 16854980 | doi = 10.1074/jbc.M605159200 | doi-access = free }}

{{Refend}}

• [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=pbd GeneReviews/NCBI/NIH/UW entry on Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum]
• [https://www.ncbi.nlm.nih.gov/omim/170993,202370,214100,266510,600279,600414,601498,601758,601789,601791,602136,602859,603164,603360,608666,170993,202370,214100,266510,600279,600414,601498,601758,601789,601791,602136,602859,603164,603360,608666 OMIM entries on Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum]