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Beyond autophagy: a novel role for autism-linked Wdfy3 in brain mitophagy
WD repeat and FYVE domain-containing 3 (WDFY3; also known as Autophagy-Linked FYVE or Alfy) is an identified intellectual disability, developmental delay and autism risk gene. This gene encodes for a scaffolding protein that is expressed in both the developing and adult central nervous system and re...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063930/ https://www.ncbi.nlm.nih.gov/pubmed/30054502 http://dx.doi.org/10.1038/s41598-018-29421-7 |
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author | Napoli, Eleonora Song, Gyu Panoutsopoulos, Alexios Riyadh, M. Asrafuzzaman Kaushik, Gaurav Halmai, Julian Levenson, Richard Zarbalis, Konstantinos S. Giulivi, Cecilia |
author_facet | Napoli, Eleonora Song, Gyu Panoutsopoulos, Alexios Riyadh, M. Asrafuzzaman Kaushik, Gaurav Halmai, Julian Levenson, Richard Zarbalis, Konstantinos S. Giulivi, Cecilia |
author_sort | Napoli, Eleonora |
collection | PubMed |
description | WD repeat and FYVE domain-containing 3 (WDFY3; also known as Autophagy-Linked FYVE or Alfy) is an identified intellectual disability, developmental delay and autism risk gene. This gene encodes for a scaffolding protein that is expressed in both the developing and adult central nervous system and required for autophagy and aggrephagy with yet unexplored roles in mitophagy. Given that mitochondrial trafficking, dynamics and remodeling have key roles in synaptic plasticity, we tested the role of Wdfy3 on brain bioenergetics by using Wdfy3(+/lacZ) mice, the only known Wdfy3 mutant animal model with overt neurodevelopmental anomalies that survive to adulthood. We found that Wdfy3 is required for sustaining brain bioenergetics and morphology via mitophagy. Decreased mitochondrial quality control by conventional mitophagy was partly compensated for by the increased formation of mitochondria-derived vesicles (MDV) targeted to lysosomal degradation (micromitophagy). These observations, extended through proteomic analysis of mitochondria-enriched cortical fractions, showed significant enrichment for pathways associated with mitophagy, mitochondrial transport and axon guidance via semaphorin, Robo, L1cam and Eph-ephrin signaling. Collectively, our findings support a critical role for Wdfy3 in mitochondrial homeostasis with implications for neuron differentiation, neurodevelopment and age-dependent neurodegeneration. |
format | Online Article Text |
id | pubmed-6063930 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60639302018-07-31 Beyond autophagy: a novel role for autism-linked Wdfy3 in brain mitophagy Napoli, Eleonora Song, Gyu Panoutsopoulos, Alexios Riyadh, M. Asrafuzzaman Kaushik, Gaurav Halmai, Julian Levenson, Richard Zarbalis, Konstantinos S. Giulivi, Cecilia Sci Rep Article WD repeat and FYVE domain-containing 3 (WDFY3; also known as Autophagy-Linked FYVE or Alfy) is an identified intellectual disability, developmental delay and autism risk gene. This gene encodes for a scaffolding protein that is expressed in both the developing and adult central nervous system and required for autophagy and aggrephagy with yet unexplored roles in mitophagy. Given that mitochondrial trafficking, dynamics and remodeling have key roles in synaptic plasticity, we tested the role of Wdfy3 on brain bioenergetics by using Wdfy3(+/lacZ) mice, the only known Wdfy3 mutant animal model with overt neurodevelopmental anomalies that survive to adulthood. We found that Wdfy3 is required for sustaining brain bioenergetics and morphology via mitophagy. Decreased mitochondrial quality control by conventional mitophagy was partly compensated for by the increased formation of mitochondria-derived vesicles (MDV) targeted to lysosomal degradation (micromitophagy). These observations, extended through proteomic analysis of mitochondria-enriched cortical fractions, showed significant enrichment for pathways associated with mitophagy, mitochondrial transport and axon guidance via semaphorin, Robo, L1cam and Eph-ephrin signaling. Collectively, our findings support a critical role for Wdfy3 in mitochondrial homeostasis with implications for neuron differentiation, neurodevelopment and age-dependent neurodegeneration. Nature Publishing Group UK 2018-07-27 /pmc/articles/PMC6063930/ /pubmed/30054502 http://dx.doi.org/10.1038/s41598-018-29421-7 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Napoli, Eleonora Song, Gyu Panoutsopoulos, Alexios Riyadh, M. Asrafuzzaman Kaushik, Gaurav Halmai, Julian Levenson, Richard Zarbalis, Konstantinos S. Giulivi, Cecilia Beyond autophagy: a novel role for autism-linked Wdfy3 in brain mitophagy |
title | Beyond autophagy: a novel role for autism-linked Wdfy3 in brain mitophagy |
title_full | Beyond autophagy: a novel role for autism-linked Wdfy3 in brain mitophagy |
title_fullStr | Beyond autophagy: a novel role for autism-linked Wdfy3 in brain mitophagy |
title_full_unstemmed | Beyond autophagy: a novel role for autism-linked Wdfy3 in brain mitophagy |
title_short | Beyond autophagy: a novel role for autism-linked Wdfy3 in brain mitophagy |
title_sort | beyond autophagy: a novel role for autism-linked wdfy3 in brain mitophagy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063930/ https://www.ncbi.nlm.nih.gov/pubmed/30054502 http://dx.doi.org/10.1038/s41598-018-29421-7 |
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