TAp73 regulates mitochondrial dynamics and multiciliated cell homeostasis through an OPA1 axis.

ABSTRACT: Dysregulated mitochondrial fusion and fission has been implicated in the pathogenesis of numerous diseases. We have identified a novel function of the p53 family protein TAp73 in regulating mitochondrial dynamics. TAp73 regulates the expression of Optic Atrophy 1 (OPA1), a protein responsible for controlling mitochondrial fusion, cristae biogenesis and electron transport chain function. Disruption of this axis results in a fragmented mitochondrial network and an impaired capacity for energy production via oxidative phosphorylation. Owing to the role of OPA1 in modulating cytochrome c release, TAp73^-/- cells display an increased sensitivity to apoptotic cell death, e.g., via BH3-mimetics. We additionally show that the TAp73/OPA1 axis has functional relevance in the upper airway,

SUBMITTER: Buckley NA 

PROVIDER: S-EPMC11549358 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature