O-GlcNAc regulates the mitochondrial integrated stress response by regulating ATF4.

ABSTRACT:

Background

Accumulation of mitochondrial dysfunctional is a hallmark of age-related neurodegeneration including Alzheimer's disease (AD). Impairment of mitochondrial quality control mechanisms leading to the accumulation of damaged mitochondria and increasing neuronal stress. Therefore, investigating the basic mechanisms of how mitochondrial homeostasis is regulated is essential. Herein, we investigate the role of O-GlcNAcylation, a single sugar post-translational modification, in controlling mitochondrial stress-induced transcription factor Activating Transcription Factor 4 (ATF4). Mitochondrial dysfunction triggers the integrated stress response (ISR^mt), in which the phosphorylation of eukaryotic translation initiation factor 2α results in the translation of ATF4.

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SUBMITTER: Alghusen IM 

PROVIDER: S-EPMC10773771 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature