Autophagy: mechanism and physiological relevance 'brewed' from yeast studies

Abstract

Autophagy is a highly conserved process of quality control occurring inside cells by which cytoplasmic material can be degraded and the products recycled for use as new building blocks or for energy production. The rapid progress and 'explosion' of knowledge concerning autophagic processes in mammals/humans that has occurred over the last 15 years was driven by fundamental studies in yeast, principally using Saccharomyces cerevisiae, leading to the identification and cloning of genes required for autophagy. This chapter reviews the role of yeast studies in understanding the molecular mechanisms of autophagic processes, focusing on aspects that are conserved in mammals/humans and how autophagy is increasingly implicated in the pathogenesis of disease and is required for development and differentiation.

Figure 1

Three main types of autophagy in yeast and mammalian cells. Three mechanistically and / or morphologically different main types of autophagy have been described in yeast and mammalian cells: Macroautophagy, microautophagy and chaperone-mediated autophagy (CMA). Macroautophagy requires autophagosome formation which is a multi-step process. The five ‘common’ complexes involved in macroautophagy (see section 6) are indicated at the step in which they participate (Boxes shaded gray). An induction signal (1) leads to the commencement of phagophore formation (2). (Note that the source of membrane for the phagophore is not shown (refer to section 5.1.) The phagophore expands (3) to eventually sequester the cargo by fusion of the phagophore ends thereby forming the double-membrane autophagosome (4). At the acid compartment (lysosome/vacuole), the outer membrane of the autophagosome fuses with the membrane and, in the case of yeast, releases a single-membrane vesicle into the lumen (5). For micro- and macroautophagy, the resident complement of acid hydrolases degrades the vesicle and its contents, or, in the case of CMA, the translocated substrates (6). The molecular ‘building blocks’ so recovered are recycled to the cytosol by efflux across the membrane (7).