Mitochondrial impairment triggers cytosolic oxidative stress and cell death following proteasome inhibition.

ABSTRACT: Dysfunctions of the mitochondria and the ubiquitin-proteasome system, as well as generation of reactive oxygen species (ROS), are linked to many aging-related neurodegenerative disorders. However, the order of these events remains unclear. Here, we show that the initial impairment occurs in mitochondria under proteasome inhibition. Fluorescent redox probe measurements revealed that proteasome inhibition led to mitochondrial oxidation followed by cytosolic oxidation, which could be prevented by a mitochondrial-targeted antioxidant or antioxidative enzyme. These observations demonstrated that proteasome dysfunction causes damage to mitochondria, leading them to increase their ROS production and resulting in cytosolic oxidation. Moreover, several antioxidants found in foods prevented intracel

SUBMITTER: Maharjan S 

PROVIDER: S-EPMC4116626 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature