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Tamargo-Gómez I, Martínez-García GG, Suárez MF, et al. ATG4D is the main ATG8 delipidating enzyme in mammalian cells and protects against cerebellar neurodegeneration. Cell Death Differ. 2021;28(9):2651-2672doi: 10.1038/s41418-021-00776-1.
Tamargo-Gómez, I., Martínez-García, G. G., Suárez, M. F., Rey, V., Fueyo, A., Codina-Martínez, H., Bretones, G., Caravia, X. M., Morel, E., Dupont, N., Cabo, R., Tomás-Zapico, C., Souquere, S., Pierron, G., Codogno, P., López-Otín, C., Fernández, �. �. F., & Mariño, G. (2021). ATG4D is the main ATG8 delipidating enzyme in mammalian cells and protects against cerebellar neurodegeneration. Cell death and differentiation, 28(9), 2651-2672. https://doi.org/10.1038/s41418-021-00776-1
Tamargo-Gómez, Isaac, et al. "ATG4D is the main ATG8 delipidating enzyme in mammalian cells and protects against cerebellar neurodegeneration." Cell death and differentiation vol. 28,9 (2021): 2651-2672. doi: https://doi.org/10.1038/s41418-021-00776-1
Tamargo-Gómez I, Martínez-García GG, Suárez MF, Rey V, Fueyo A, Codina-Martínez H, Bretones G, Caravia XM, Morel E, Dupont N, Cabo R, Tomás-Zapico C, Souquere S, Pierron G, Codogno P, López-Otín C, Fernández ÁF, Mariño G. ATG4D is the main ATG8 delipidating enzyme in mammalian cells and protects against cerebellar neurodegeneration. Cell Death Differ. 2021 Sep;28(9):2651-2672. doi: 10.1038/s41418-021-00776-1. Epub 2021 Apr 01. PMID: 33795848; PMCID: PMC8408152.
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Cell Death Differ. 2021 Sep;28(9):2651-2672. doi: 10.1038/s41418-021-00776-1. Epub 2021 Apr 01.

ATG4D is the main ATG8 delipidating enzyme in mammalian cells and protects against cerebellar neurodegeneration.

Cell death and differentiation

Isaac Tamargo-Gómez, Gemma G Martínez-García, María F Suárez, Verónica Rey, Antonio Fueyo, Helena Codina-Martínez, Gabriel Bretones, Xurde M Caravia, Etienne Morel, Nicolas Dupont, Roberto Cabo, Cristina Tomás-Zapico, Sylvie Souquere, Gerard Pierron, Patrice Codogno, Carlos López-Otín, Álvaro F Fernández, Guillermo Mariño

Affiliations

  1. Departamento de Biología Funcional, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain.
  2. Instituto Universitario de Oncología (IUOPA), Asturias, Spain.
  3. Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Asturias, Spain.
  4. Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo, Oviedo, Spain.
  5. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
  6. U1151 and Institut Necker Enfants-Malades, INSERM, Sorbonne Paris Cité, Université Paris Descartes, Paris, France.
  7. Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain.
  8. Gustave Roussy Comprehensive Cancer Center, Villejuif, France.
  9. CNRS, Villejuif, France.
  10. Departamento de Biología Funcional, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain. [email protected].
  11. Instituto Universitario de Oncología (IUOPA), Asturias, Spain. [email protected].
  12. Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Asturias, Spain. [email protected].

PMID: 33795848 PMCID: PMC8408152 DOI: 10.1038/s41418-021-00776-1

Abstract

Despite the great advances in autophagy research in the last years, the specific functions of the four mammalian Atg4 proteases (ATG4A-D) remain unclear. In yeast, Atg4 mediates both Atg8 proteolytic activation, and its delipidation. However, it is not clear how these two roles are distributed along the members of the ATG4 family of proteases. We show that these two functions are preferentially carried out by distinct ATG4 proteases, being ATG4D the main delipidating enzyme. In mammalian cells, ATG4D loss results in accumulation of membrane-bound forms of mATG8s, increased cellular autophagosome number and reduced autophagosome average size. In mice, ATG4D loss leads to cerebellar neurodegeneration and impaired motor coordination caused by alterations in trafficking/clustering of GABA

© 2021. The Author(s).

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