Skip to main content
eScholarship
Open Access Publications from the University of California

UC Davis

UC Davis Previously Published Works bannerUC Davis

Wdfy3 regulates glycophagy, mitophagy, and synaptic plasticity.

  • Author(s): Napoli, Eleonora;
  • Panoutsopoulos, Alexios A;
  • Kysar, Patricia;
  • Satriya, Nathaniel;
  • Sterling, Kira;
  • Shibata, Bradley;
  • Imai, Denise;
  • Ruskin, David N;
  • Zarbalis, Konstantinos S;
  • Giulivi, Cecilia
  • et al.

Published Web Location

https://journals.sagepub.com/doi/10.1177/0271678X211027384
No data is associated with this publication.
Abstract

Autophagy is essential to cell function, as it enables the recycling of intracellular constituents during starvation and in addition functions as a quality control mechanism by eliminating spent organelles and proteins that could cause cellular damage if not properly removed. Recently, we reported on Wdfy3's role in mitophagy, a clinically relevant macroautophagic scaffold protein that is linked to intellectual disability, neurodevelopmental delay, and autism spectrum disorder. In this study, we confirm our previous report that Wdfy3 haploinsufficiency in mice results in decreased mitophagy with accumulation of mitochondria with altered morphology, but expanding on that observation, we also note decreased mitochondrial localization at synaptic terminals and decreased synaptic density, which may contribute to altered synaptic plasticity. These changes are accompanied by defective elimination of glycogen particles and a shift to increased glycogen synthesis over glycogenolysis and glycophagy. This imbalance leads to an age-dependent higher incidence of brain glycogen deposits with cerebellar hypoplasia. Our results support and further extend Wdfy3's role in modulating both brain bioenergetics and synaptic plasticity by including glycogen as a target of macroautophagic degradation.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Item not freely available? Link broken?
Report a problem accessing this item