Mutant ubiquitin UBB+1 induces mitochondrial fusion by destabilizing mitochondrial fission-specific proteins and confers resistance to oxidative stress-induced cell death in astrocytic cells.

ABSTRACT: Mutant ubiquitin UBB+1 is observed in a variety of aging-related neurodegenerative diseases and acts as a potent inhibitor of the ubiquitin proteasome system (UPS). In the present study, we investigated the relationship between impaired UPS (using ectopic expression of UBB+1) and mitochondrial dynamics in astrocytes, which are the most abundant glial cells in the central nervous system. Immunocytochemistry and fluorescence recovery after photobleaching revealed that ectopic expression of UBB+1 induced mitochondrial elongation. We further demonstrated that overexpression of UBB+1 destabilized mitochondrial fission-specific proteins including Drp1, Fis1, and OPA3, but not the mitochondrial fusion-specific proteins Mfn1, Mfn2, and OPA1. The reduction in mitochondrial fission-specific proteins

SUBMITTER: Yim N 

PROVIDER: S-EPMC4062464 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature