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Napoli E, Panoutsopoulos AA, Kysar P, et al. Wdfy3 regulates glycophagy, mitophagy, and synaptic plasticity. J Cereb Blood Flow Metab. 2021;41(12):3213-3231doi: 10.1177/0271678X211027384.
Napoli, E., Panoutsopoulos, A. A., Kysar, P., Satriya, N., Sterling, K., Shibata, B., Imai, D., Ruskin, D. N., Zarbalis, K. S., & Giulivi, C. (2021). Wdfy3 regulates glycophagy, mitophagy, and synaptic plasticity. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 41(12), 3213-3231. https://doi.org/10.1177/0271678X211027384
Napoli, Eleonora, et al. "Wdfy3 regulates glycophagy, mitophagy, and synaptic plasticity." Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism vol. 41,12 (2021): 3213-3231. doi: https://doi.org/10.1177/0271678X211027384
Napoli E, Panoutsopoulos AA, Kysar P, Satriya N, Sterling K, Shibata B, Imai D, Ruskin DN, Zarbalis KS, Giulivi C. Wdfy3 regulates glycophagy, mitophagy, and synaptic plasticity. J Cereb Blood Flow Metab. 2021 Dec;41(12):3213-3231. doi: 10.1177/0271678X211027384. Epub 2021 Jun 29. PMID: 34187232; PMCID: PMC8669292.
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J Cereb Blood Flow Metab. 2021 Dec;41(12):3213-3231. doi: 10.1177/0271678X211027384. Epub 2021 Jun 29.

Wdfy3 regulates glycophagy, mitophagy, and synaptic plasticity.

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

Eleonora Napoli, Alexios A Panoutsopoulos, Patricia Kysar, Nathaniel Satriya, Kira Sterling, Bradley Shibata, Denise Imai, David N Ruskin, Konstantinos S Zarbalis, Cecilia Giulivi

Affiliations

  1. Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
  2. Department of Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA, USA.
  3. Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Sacramento, CA, USA.
  4. Department of Cell Biology and Human Anatomy, School of Medicine, University of California, Davis, CA, USA.
  5. Anatomic Pathology Service, Veterinary Medical Teaching Hospital, University of California, Davis, CA, USA.
  6. Department of Psychology and Neuroscience Program, Trinity College, Hartford, CT, USA.
  7. Medical Investigations of Neurodevelopmental Disorders (MIND) Institute, University of California Davis, CA, USA.

PMID: 34187232 PMCID: PMC8669292 DOI: 10.1177/0271678X211027384

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.

Keywords: Glycogen; brain; electron microscopy; mitochondria; synapses

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