MITOCHONDRIAL CHANGES AND OXIDATIVE STRESS IN A MOUSE MODEL OF ZELLWEGER SYNDROME NEUROPATHOGENESIS

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 mitochondria! population. Cultured fibroblasts from PEX13-deficient mouse embryo displayed similar changes, as well as increased levels of mitochondria! 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 mitochondria! oxidative stress and aberrant mitochondrial dynamics are associated with the neuropathology arising from PEX13 deficiency. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.