The impact of ER^UPR on mitochondrial integrity mediated by PDK4.

ABSTRACT: ER and mitochondrial stress are often interconnected and considered major contributors to aging as well as neurodegeneration. Coordinated induction of ER^UPR and mito^UPR has been observed in diabetes and pulmonary disorders. However, in the context of aging and neurodegeneration, regulation of this intra-organellar crosstalk has remained relatively elusive. Here, we demonstrate that pyruvate dehydrogenase kinase 4 (PDK4), a mitochondrial protein, accumulates at the ER-mitochondrial contact sites (MAMs) during ER stress. Classically, PDK4 is known to phosphorylate PDHA1 (pyruvate dehydrogenase E1 subunit alpha 1) and plays a significant role in regulating the oxidative phosphorylation-driven ATP production. In this study, we propose a non-canonical kinase-independent fu

SUBMITTER: Mallick P 

PROVIDER: S-EPMC12307875 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature