PML at Mitochondria-Associated Membranes Is Critical for the Repression of Autophagy and Cancer Development

Sonia Missiroli (1) , Massimo Bonora (1) , Simone Patergnani (1) , Federica Poletti (1) , Mariasole Perrone (1) , Roberta Gafà (1) , Eros Magri (1) , Andrea Raimondi (2) , Giovanni Lanza (1) , Carlo Tacchetti (3, 2) , Guido Kroemer (4, 5, 6, 7) , Pier Paolo Pandolfi (8) , Paolo Pinton (1) , Carlotta Giorgi (1)

1 UniFE - Università degli Studi di Ferrara = University of Ferrara
2 San Raffaele Scientific Institute
3 UniGe - Università degli studi di Genova = University of Genoa
4 Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138 - Apoptose, cancer et immunité
5 IGR - Institut Gustave Roussy
6 Service de biologie [CHU HEGP]
7 Karolinska Institutet [Stockholm]
8 HMS - Harvard Medical School [Boston]

The precise molecular mechanisms that coordinate apoptosis and autophagy in cancer remain to be determined. Here, we provide evidence that the tumor suppressor promyelocytic leukemia protein (PML) controls autophagosome formation at mitochondria-associated membranes (MAMs) and, thus, autophagy induction. Our in vitro and in vivo results demonstrate how PML functions as a repressor of autophagy. PML loss promotes tumor development, providing a growth advantage to tumor cells that use autophagy as a cell survival strategy during stress conditions. These findings demonstrate that autophagy inhibition could be paired with a chemotherapeutic agent to develop anticancer strategies for tumors that present PML downregulation.

Domaines: Cancer

Sonia Missiroli, Massimo Bonora, Simone Patergnani, Federica Poletti, Mariasole Perrone, et al.. PML at Mitochondria-Associated Membranes Is Critical for the Repression of Autophagy and Cancer Development. Cell Reports, 2016, 16 (9), pp.2415 - 2427. ⟨10.1016/j.celrep.2016.07.082⟩. ⟨hal-01375400⟩