Abstract

Autophagy is an evolutionary conserved catabolic process involved in several physiological and pathological processes such as cancer and neurodegeneration. Autophagy initiation signaling requires both the ULK1 kinase and the BECLIN 1-VPS34 core complex to generate autophagosomes, double-membraned vesicles that transfer cellular contents to lysosomes. In this study, we show that the BECLIN 1-VPS34 complex is tethered to the cytoskeleton through an interaction between the BECLIN 1-interacting protein AMBRA1 and dynein light chains 1/2. When autophagy is induced, ULK1 phosphorylates AMBRA1, releasing the autophagy core complex from dynein. Its subsequent relocalization to the endoplasmic reticulum enables autophagosome nucleation. Therefore, AMBRA1 constitutes a direct regulatory link between ULK1 and BECLIN 1-VPS34, which is required for core complex positioning and activity within the cell. Moreover, our results demonstrate that in addition to a function for microtubules in mediating autophagosome transport, there is a strict and regulatory relationship between cytoskeleton dynamics and autophagosome formation.

Autore Pugliese

• Fimia Gian Maria

Tutti gli autori

• Di Bartolomeo S. , Corazzari M. , Nazio F. , Oliverio S. , Lisi G. , Antonioli M. , Pagliarini V. , Matteoni S. , Fuoco C. , Giunta L. , D'Amelio M. , Nardacci R. , Romagnoli A. , Piacentini M. , Cecconi F. , Fimia G.M.

Titolo volume/Rivista

THE JOURNAL OF CELL BIOLOGY

Anno di pubblicazione

2010

ISSN

0021-9525

ISBN

Non Disponibile

Numero di citazioni Wos

211

Ultimo Aggiornamento Citazioni

25/04/2018

Numero di citazioni Scopus

227

Ultimo Aggiornamento Citazioni

26/04/2018

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile