%0 Journal Article
%T Zymophagy: Selective Autophagy of Secretory Granules
%A Maria I. Vaccaro
%J International Journal of Cell Biology
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/396705
%X Timing is everything. That¡¯s especially true when it comes to the activation of enzymes created by the pancreas to break down food. Pancreatic enzymes are packed in secretory granules as precursor molecules called zymogens. In physiological conditions, those zymogens are activated only when they reach the gut, where they get to work releasing and distributing nutrients that we need to survive. If this process fails and the enzymes are prematurely activated within the pancreatic cell, before they are released from the gland, they break down the pancreas itself causing acute pancreatitis. This is a painful disease that ranges from a mild and autolimited process to a severe and lethal condition. Recently, we demonstrated that the pancreatic acinar cell is able to switch on a refined mechanism that could explain the autolimited form of the disease. This is a novel selective form of autophagy named zymophagy, a cellular process to specifically detect and degrade secretory granules containing activated enzymes before they can digest the organ. In this work, we revise the molecules and mechanisms that mediate zymophagy, a selective autophagy of secretory granules. 1. Introduction Autophagy is an evolutionarily preserved cellular process that is responsible for the degradation of long-lived proteins and entire organelles to maintain intracellular homeostasis and to contribute to starvation and stress responses. Macroautophagy involves the formation of double-membrane autophagosomes around cargoes, including larger structures such as organelles and protein aggregates. Autophagosomes then fuse with lysosomes, where the degradation of the cargoes takes place. Both nonselective bulk autophagy and selective autophagy of specific proteins and organelles have been described [1]. Genetic analyses in yeast identified more than 30 conserved components that are required for different steps of autophagy (termed Atg genes) [2]. Recently, several lines of evidence suggest the existence of selective autophagic degradation pathways in physiology and disease, named, selective autophagy [3]. During selective autophagy, single cellular structures, such as protein aggregates and mitochondria are specifically sequestered by autophagosomes. There is emerging evidence suggesting the involvement of ubiquitin in several forms of selective autophagy process. For example, aggregate clearance by autophagy requires ubiquitylation and ubiquitin-binding receptors such as p62 (also known as SQSTM1) [4]. Ubiquitylated artificial substrates are recognized by the autophagy machinery and are
%U http://www.hindawi.com/journals/ijcb/2012/396705/