Chronic and age-dependent effects of the spongiform neurodegeneration-associated MGRN1 E3 ubiquitin ligase on mitochondrial homeostasis.

ABSTRACT: Spongiform encephalopathy is an intriguing yet poorly understood neuropathology characterized by vacuoles, demyelination, and gliosis. It is observed in patients with prion disease, primary mitochondrial disease, HIV-1 infection of the brain, and some inherited disorders, but the underlying mechanism of disease remains unclear. The brains of mice lacking the MGRN1 E3 ubiquitin ligase develop vacuoles by 9 months of age. MGRN1-dependent ubiquitination has been reported to regulate mitofusin 1 and GP78, suggesting MGRN1 may have a direct effect on mitochondrial homeostasis. Here, we demonstrate that some MGRN1 localizes to mitochondria, most likely due to N-myristoylation, and mitochondria in cells from Mgrn1 null mutant mice display fragmentation and depolarization without recruitment of th

SUBMITTER: Gunn TM 

PROVIDER: S-EPMC6639055 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature