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

Vicencio, JM; Ortiz, C.; Criollo, A; Jones, AWE; Kepp, O; Galluzzi L.; Joza, N; Vitale, I; Morselli E.; Tailler, M; Castedo, M; Maiuri, MC; Molgó J.; Szabadkai G.; Lavandero S.; et. al.

Abstract

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.

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Título según WOS: The inositol 1,4,5-trisphosphate receptor regulates autophagy through its interaction with Beclin 1
Título según SCOPUS: The inositol 1,4,5-trisphosphate receptor regulates autophagy through its interaction with Beclin 1
Título de la Revista: CELL DEATH AND DIFFERENTIATION
Volumen: 16
Número: 7
Editorial: Nature Publishing Group
Fecha de publicación: 2009
Página de inicio: 1006
Página final: 1017
Idioma: English
URL: http://www.nature.com/doifinder/10.1038/cdd.2009.34
DOI:

10.1038/cdd.2009.34

Notas: ISI, SCOPUS