"Paper of the Week" Zymophagy, a novel selective autophagy pathway mediated by VMP1-USP9x-p62, prevents pancreatic cell death. (citado 13 veces al 2-Nov-2012, h index=14)

GRASSO D; ROPOLO A; LO RE A; BOGGIO V; MOLEJÓN MI; IOVANNA JL; GONZALEZ CD; URRUTIA R; VACCARO MI

JOURNAL OF BIOLOGICAL CHEMISTRY

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Lugar: Rockville, Maryland 20852-3110 ; Año: 2011 vol. 286 p. 8308 - 8324

0021-9258

Este trabajo publicado en 2011, fue citado 13 veces segun Scopus al 2 de noviembre de 2012, fue premiado por la Academia Nacional de Medicina, originó un número conferencias y trabajos de revisión. Zymophagy, a Novel Selective Autophagy Pathway Mediated by VMP1-USP9x-p62, Prevents Pancreatic Cell Death*♦ Daniel Grasso?,1, Alejandro Ropolo?, Andrea Lo Ré?,2, Verónica Boggio?, María I. Molejón?,3, Juan L. Iovanna§, Claudio D. Gonzalez?, Raúl Urrutia¶ and María I. Vaccaro?,4 + Author Affiliations From the ?Department of Pathophysiology, School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD Buenos Aires, Argentina, the §Unité 624, INSERM, 13288 Marseille, France, and the ¶Chromatin Dynamics and Epigenetic Laboratory, Mayo Clinic, Rochester, Minnesota 55905 4 To whom correspondence should be addressed: School of Pharmacy and Biochemistry, University of Buenos Aires, 956 Junín, C1113AAD Buenos Aires, Argentina. Tel.: 5411-4964-8368; Fax: 5411-4968-8268; E-mail: mvaccaro@ffyb.uba.ar.  Next Section Abstract Autophagy has recently elicited significant attention as a mechanism that either protects or promotes cell death, although different autophagy pathways, and the cellular context in which they occur, remain to be elucidated. We report a thorough cellular and biochemical characterization of a novel selective autophagy that works as a protective cell response. This new selective autophagy is activated in pancreatic acinar cells during pancreatitis-induced vesicular transport alteration to sequester and degrade potentially deleterious activated zymogen granules. We have coined the term ?zymophagy? to refer to this process. The autophagy-related protein VMP1, the ubiquitin-protease USP9x, and the ubiquitin-binding protein p62 mediate zymophagy. Moreover, VMP1 interacts with USP9x, indicating that there is a close cooperation between the autophagy pathway and the ubiquitin recognition machinery required for selective autophagosome formation. Zymophagy is activated by experimental pancreatitis in genetically engineered mice and cultured pancreatic acinar cells and by acute pancreatitis in humans. Furthermore, zymophagy has pathophysiological relevance by controlling pancreatitis-induced intracellular zymogen activation and helping to prevent cell death. Together, these data reveal a novel selective form of autophagy mediated by the VMP1-USP9x-p62 pathway, as a cellular protective response.