title: Mitochondrial changes and oxidative stress in a mouse model of Zellweger syndrome neuropathogenesis.
abstract: Zellweger syndrome (ZS) is a peroxisome biogenesis disorder that involves significant neuropathology, the molecular basis of which is still poorly understood. Using a mouse model of ZS with brain-restricted deficiency of the peroxisome biogenesis protein PEX13, we demonstrated an expanded and morphologically modified brain mitochondrial population. Cultured fibroblasts from PEX13-deficient mouse embryo displayed similar changes, as well as increased levels of mitochondrial superoxide and membrane depolarization; this phenotype was rescued by antioxidant treatment. Significant oxidative damage to neurons in brain was indicated by products of lipid and DNA oxidation. Similar overall changes were observed for glial cells. In toto, these findings suggest that mitochondrial oxidative stress and aberrant mitochondrial dynamics are associated with the neuropathology arising from PEX13 deficiency.
authors: Eskitis Institute for Drug Discovery, and School of Natural Sciences, Griffith University, Qld, Australia.
authors: Rani Sadia
authors: RS
authors: Rahim
authors: Eskitis Institute for Drug Discovery, and School of Natural Sciences, Griffith University, Qld, Australia.
authors: Mo
authors: M
authors: Chen
authors: Eskitis Institute for Drug Discovery, and School of Natural Sciences, Griffith University, Qld, Australia.
authors: C Cathrin
authors: CC
authors: Nourse
authors: Griffith Health Institute, School of Medical Science, Griffith University, Qld, Australia.
authors: Adrian C B
authors: AC
authors: Meedeniya
authors: Eskitis Institute for Drug Discovery, and School of Natural Sciences, Griffith University, Qld, Australia. Electronic address: d.crane@griffith.edu.au.
authors: Denis I
authors: DI
authors: Crane
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D015211:Zellweger Syndrome / Q000378:metabolism* / Q000473:pathology; D000099156:Superoxide Dismutase 2
chemical_list: D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D013482:Superoxide Dismutase; D014365:Tryptophan Hydroxylase; D000099156:Superoxide Dismutase 2; C491106:Pex13 protein, mouse; C528900:glial fibrillary astrocytic protein, mouse; C487802:Tph2 protein, mouse
keywords: PEX13 deficiency; Zellweger syndrome; mitochondria; oxidative stress; peroxisomes