PML at Mitochondria-Associated Membranes Is Critical for the Repression of Autophagy and Cancer Development
Sonia Missiroli,
Massimo Bonora,
Simone Patergnani,
Federica Poletti,
Mariasole Perrone,
Roberta Gafà,
Eros Magri,
Andrea Raimondi,
Giovanni Lanza,
Carlo Tacchetti,
Guido Kroemer,
Pier Paolo Pandolfi,
Paolo Pinton,
Carlotta Giorgi
Affiliations
Sonia Missiroli
Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology and LTTA Center, University of Ferrara, Ferrara 44121, Italy
Massimo Bonora
Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology and LTTA Center, University of Ferrara, Ferrara 44121, Italy
Simone Patergnani
Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology and LTTA Center, University of Ferrara, Ferrara 44121, Italy
Federica Poletti
Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology and LTTA Center, University of Ferrara, Ferrara 44121, Italy
Mariasole Perrone
Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology and LTTA Center, University of Ferrara, Ferrara 44121, Italy
Roberta Gafà
Department of Morphology, Surgery and Experimental Medicine, Section of Anatomic Pathology and Molecular Diagnostics, University of Ferrara, Ferrara 44121, Italy
Eros Magri
Department of Morphology, Surgery and Experimental Medicine, Section of Anatomic Pathology and Molecular Diagnostics, University of Ferrara, Ferrara 44121, Italy
Andrea Raimondi
Experimental Imaging Center, San Raffaele Scientific Institute, Milan 20132, Italy
Giovanni Lanza
Department of Morphology, Surgery and Experimental Medicine, Section of Anatomic Pathology and Molecular Diagnostics, University of Ferrara, Ferrara 44121, Italy
Carlo Tacchetti
Experimental Imaging Center, San Raffaele Scientific Institute, Milan 20132, Italy
Guido Kroemer
Equipe 11 Labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris 75006, France
Pier Paolo Pandolfi
Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, MA 02215, USA
Paolo Pinton
Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology and LTTA Center, University of Ferrara, Ferrara 44121, Italy
Carlotta Giorgi
Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology and LTTA Center, University of Ferrara, Ferrara 44121, Italy
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.
