The inositol 1,4,5-trisphosphate receptor regulates autophagy through its interaction with Beclin 1

J. M. Vicencio, C. Ortiz, A. Criollo, A. W.E. Jones, O. Kepp, L. Galluzzi, N. Joza, I. Vitale, E. Morselli, M. Tailler, M. Castedo, M. C. Maiuri, J. Molgó, G. Szabadkai, S. Lavandero, G. Kroemer

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256 Citas (Scopus)

Resumen

The inositol 1,4,5-trisphosphate receptor (IP3R) is a major regulator of apoptotic signaling. Through interactions with members of the Bcl-2 family of proteins, it drives calcium (Ca2+) transients from the endoplasmic reticulum (ER) to mitochondria, thereby establishing a functional and physical link between these organelles. Importantly, the IP3R also regulates autophagy, and in particular, its inhibition/depletion strongly induces macroautophagy. Here, we show that the IP3R antagonist xestospongin B induces autophagy by disrupting a molecular complex formed by the IP3 R and Beclin 1, an interaction that is increased or inhibited by overexpression or knockdown of Bcl-2, respectively. An effect of Beclin 1 on Ca2+ homeostasis was discarded as siRNA-mediated knockdown of Beclin 1 did not affect cytosolic or luminal ER Ca2+ levels. Xestospongin B- or starvation-induced autophagy was inhibited by overexpression of the IP3R ligand-binding domain, which coimmunoprecipitated with Beclin 1. These results identify IP3R as a new regulator of the Beclin 1 complex that may bridge signals converging on the ER and initial phagophore formation.

Idioma originalEnglish
Páginas (desde-hasta)1006-1017
Número de páginas12
PublicaciónCell Death and Differentiation
Volumen16
N.º7
DOI
EstadoPublished - 2009

Financiación

FinanciadoresNúmero del financiador
Cancéropôle Ile-de-France
European Commission
Agence Nationale de la Recherche
Comisión Nacional de Investigación Científica y Tecnológica
Fondation pour la Recherche Médicale
EMBO
Ligue Contre le Cancer
Right to Care

    ASJC Scopus Subject Areas

    • Molecular Biology
    • Cell Biology

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    Profundice en los temas de investigación de 'The inositol 1,4,5-trisphosphate receptor regulates autophagy through its interaction with Beclin 1'. En conjunto forman una huella única.

    Citar esto

    Vicencio, J. M., Ortiz, C., Criollo, A., Jones, A. W. E., Kepp, O., Galluzzi, L., Joza, N., Vitale, I., Morselli, E., Tailler, M., Castedo, M., Maiuri, M. C., Molgó, J., Szabadkai, G., Lavandero, S., & Kroemer, G. (2009). The inositol 1,4,5-trisphosphate receptor regulates autophagy through its interaction with Beclin 1. Cell Death and Differentiation, 16(7), 1006-1017. https://doi.org/10.1038/cdd.2009.34