ANALISIS DE LAS FUNCIONES DE LA AUTOFAGIA EN EL ENVEJECIMIENTO MEDIANTE ANALISIS DE MODELOS DEFICIENTES EN PROTEASAS ATG4

PID2021-127534OB-I00

Nombre agencia financiadora Agencia Estatal de Investigación
Acrónimo agencia financiadora AEI
Programa Programa Estatal para Impulsar la Investigación Científico-Técnica y su Transferencia
Subprograma Subprograma Estatal de Generación de Conocimiento
Convocatoria Proyectos de I+D+I (Generación de Conocimiento y Retos Investigación)
Año convocatoria 2021
Unidad de gestión Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023
Centro beneficiario FUNDACION PARA LA INVESTIGACION E INNOVACION BIOSANITARIA EN EL PRINCIPADO DE ASTURIAS
Identificador persistente http://dx.doi.org/10.13039/501100011033

Publicaciones

Found(s) 2 result(s)
Found(s) 1 page(s)

Analysis of ATG4C function in vivo

Digital.CSIC. Repositorio Institucional del CSIC
  • Tamargo-Gómez, Isaac
  • Martínez-García, Gemma G.
  • Suárez, María F.
  • Mayoral, Pablo
  • Bretones, Gabriel
  • Astudillo, Aurora
  • Prieto-Lloret, Jesús
  • Sveen, Christina
  • Fueyo, Antonio
  • Engedal, Nikolai
  • López-Otín, Carlos
  • Mariño, Guillermo
Despite the great advances in macroautophagy/autophagy research in the last years, the in vivo role of the different members of the four mammalian orthologs of yeast Atg4 protease (ATG4A-D) remain unclear. To gain further insights into the functional relevance of Atg4 orthologs, we have generated mutant mice deficient in Atg4c. These mice are viable and fertile, and do not display any obvious abnormalities, indicating that they are able to develop the autophagic response required during the early neonatal period. However, they show tissue-specific autophagy alterations, including reduced autophagic flux in diaphragm and show decreased breathing and locomotor activity after fasting. In addition, atg4c-/- mice show reduced number of circulating T and B lymphocytes, which is associated with accumulation of apoptotic cells in the spleen and an increased susceptibility to develop chemically-induced fibrosarcomas. Moreover, through the analysis of cells and mice simultaneously deficient for ATG4C and ATG4D proteases we also reveal a role for ATG4C in mATG8 proteins delipidation., This work was supported by grants from Ministerio Ciencia eInnovación (Spain) (PID2021-127534OB-I00), the South-Eastern 1315 Norway Regional Health Authority (2021088 to N.E.) and Instituto de Salud Carlos III (RTICC Spain). Jesús Prieto-Lloret is funded by Programa Estrategico IBGM, Escalera de Excelencia, ref. CCVC8485, Consejería de
Educación, Junta de Castilla y León (Spain). Funding for open Access Charge: Roche Farma”, as the aricle will be published via Open access and the OA costs will be funded by Roche Farma., Peer reviewed




Tamargo-Gómez, Isaac; Martínez-García, Gemma G.; Suárez, María F.; Mayoral, Pablo; Bretones, Gabriel; Astudillo, Aurora; Prieto-Lloret, Jesús; Sveen, Christina; Fueyo, Antonio; Engedal, Nikolai; López-Otín, Carlos; Mariño, Guillermo

Digital.CSIC. Repositorio Institucional del CSIC
  • Tamargo-Gómez, Isaac
  • Martínez-García, Gemma G.
  • Suárez, María F.
  • Mayoral, Pablo
  • Bretones, Gabriel
  • Astudillo, Aurora
  • Prieto-Lloret, Jesús
  • Sveen, Christina
  • Fueyo, Antonio
  • Engedal, Nikolai
  • López-Otín, Carlos
  • Mariño, Guillermo
Despite the great advances in macroautophagy/autophagy research in the last years, the in vivo role of the different members of the four mammalian orthologs of yeast Atg4 protease (ATG4A-D) remain unclear. To gain further insights into the functional relevance of Atg4 orthologs, we have generated mutant mice deficient in Atg4c. These mice are viable and fertile, and do not display any obvious abnormalities, indicating that they are able to develop the autophagic response required during the early neonatal period. However, they show tissue-specific autophagy alterations, including reduced autophagic flux in diaphragm and show decreased breathing and locomotor activity after fasting. In addition, atg4c-/- mice show reduced number of circulating T and B lymphocytes, which is associated with accumulation of apoptotic cells in the spleen and an increased susceptibility to develop chemically-induced fibrosarcomas. Moreover, through the analysis of cells and mice simultaneously deficient for ATG4C and ATG4D proteases we also reveal a role for ATG4C in mATG8 proteins delipidation.

ATG4 (autophagy related 4 cysteine peptidase); ATG4A (autophagy related 4A cysteine peptidase); ATG4B (autophagy related 4B cysteine peptidase); ATG4C (autophagy related 4C cysteine peptidase); ATG4D (autophagy related 4D cysteine peptidase); Atg8 (autophagy related 8); GABARAP (GABA type A receptor-associated protein); GABARAPL1(GABA type A receptor-associated protein like 1); GABARAPL2 (GABA type A receptor-associated protein like 2); MAP1LC3A/LC3A (microtubule associated protein 1 light chain 3 alpha); MAP1LC3B/LC3B (microtubule associated protein 1 light chain 3 beta); mATG8 (mammalian Atg8); PE (phosphatidylethanolamine); PS (phosphatydylserine); SQSTM1/p62 (sequestosome 1)., This work was supported by grants from Ministerio Ciencia eInnovación (Spain) (PID2021-127534OB-I00), the South-Eastern 1315 Norway Regional Health Authority (2021088 to N.E.) and Instituto de Salud Carlos III (RTICC Spain). Jesús Prieto-Lloret is funded by Programa Estrategico IBGM, Escalera de Excelencia, ref. CCVC8485, Consejería de Educación, Junta de Castilla y León (Spain). Funding for open Access Charge: Roche Farma”, as the aricle will be published via Open access and the OA costs will be funded by Roche Farma., Peer reviewed