Reactive oxygen species control protein degradation at the mitochondrial import gate.

ABSTRACT: While reactive oxygen species (ROS) have long been known to drive aging and neurodegeneration, their persistent depletion below basal levels also disrupts organismal function. Cells counteract loss of basal ROS via the reductive stress response, but the identity and biochemical activity of ROS sensed by this pathway remain unknown. Here, we show that the central enzyme of the reductive stress response, the E3 ligase Cullin 2-FEM1 homolog B (CUL2^FEM1B), specifically acts at mitochondrial TOM complexes, where it senses ROS produced by complex III of the electron transport chain (ETC). ROS depletion during times of low ETC activity triggers the localized degradation of CUL2^FEM1B substrates, which sustains mitochondrial import and ensures the biogenesis of the rate-limiti

SUBMITTER: McMinimy R 

PROVIDER: S-EPMC11649020 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature