Raft-like lipid microdomains drive autophagy initiation via AMBRA1-ERLIN1 molecular association within MAMs

Manganelli, Valeria; Matarrese, Paola; Antonioli, Manuela; Gambardella, Lucrezia; Vescovo, Tiziana; Gretzmeier, Christine; Longo, Agostina; Capozzi, Antonella; Recalchi, Serena; Riitano, Gloria; Misasi, Roberta; Dengjel, Jörn; Malorni, Walter; Fimia, Gian Maria; Sorice, Maurizio; Garofalo, Tina

doi:10.1080/15548627.2020.1834207

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Raft-like lipid microdomains drive autophagy initiation via AMBRA1-ERLIN1 molecular association within MAMs

Manganelli, Valeria Department of Experimental Medicine, Sapienza University , Rome, Italy
Matarrese, Paola Oncology Unit, Center for Gender-Specific Medicine, Istituto Superiore di Sanità , Rome, Italy
Antonioli, Manuela Department of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS , Rome, Italy
Gambardella, Lucrezia Oncology Unit, Center for Gender-Specific Medicine, Istituto Superiore di Sanità , Rome, Italy
Vescovo, Tiziana Department of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS , Rome, Italy
Gretzmeier, Christine Department of Dermatology, Faculty of Medicine, Medical Center-University of Freiburg , Freiburg, Germany
Longo, Agostina Department of Experimental Medicine, Sapienza University , Rome, Italy
Capozzi, Antonella Department of Experimental Medicine, Sapienza University , Rome, Italy
Recalchi, Serena Department of Experimental Medicine, Sapienza University , Rome, Italy
Riitano, Gloria Department of Experimental Medicine, Sapienza University , Rome, Italy
Misasi, Roberta Department of Experimental Medicine, Sapienza University , Rome, Italy
Dengjel, Jörn Department of Dermatology, Faculty of Medicine, Medical Center-University of Freiburg , Freiburg, Germany - Department of Biology, University of Fribourg , Suisse, Germany
Malorni, Walter School of Pharmacy, University of Tor Vergata , Rome, Italy
Fimia, Gian Maria Department of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS , Rome, Italy - Department of Molecular Medicine, Sapienza University , Rome, Italy
Sorice, Maurizio Department of Experimental Medicine, Sapienza University , Rome, Italy
Garofalo, Tina Department of Experimental Medicine, Sapienza University , Rome, Italy

09.10.2020

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Autophagy. - 2020, p. 1-21

English Mitochondria-associated membranes (MAMs) are essential communication subdomains of the endoplasmic reticulum (ER) that interact with mitochondria. We previously demonstrated that, upon macroautophagy/autophagy induction, AMBRA1 is recruited to the BECN1 complex and relocalizes to MAMs, where it regulates autophagy by interacting with raft-like components. ERLIN1 is an endoplasmic reticulum lipid raft protein of the prohibitin family. However, little is known about its association with the MAM interface and its involvement in autophagic initiation. In this study, we investigated ERLIN1 association with MAM raft-like microdomains and its interaction with AMBRA1 in the regulation of the autophagic process. We show that ERLIN1 interacts with AMBRA1 at MAM raft-like microdomains, which represents an essential condition for autophagosome formation upon nutrient starvation, as demonstrated by knocking down ERLIN1 gene expression. Moreover, this interaction depends on the “integrity” of key molecules, such as ganglioside GD3 and MFN2. Indeed, knocking down ST8SIA1/GD3-synthase or MFN2 expression impairs AMBRA1-ERLIN1 interaction at the MAM level and hinders autophagy. In conclusion, AMBRA1-ERLIN1 interaction within MAM raft-like microdomains appears to be pivotal in promoting the formation of autophagosomes.

Faculty

Faculté des sciences et de médecine

Department

Département de Biologie

Language