An overview of macroautophagy in yeast

Abstract

Macroautophagy is an evolutionarily conserved dynamic pathway that functions primarily in a degradative manner. A basal level of macroautophagy occurs constitutively, but this process can be further induced in response to various types of stress including starvation, hypoxia and hormonal stimuli. The general principle behind macroautophagy is that cytoplasmic contents can be sequestered within a transient double-membrane organelle, an autophagosome, which subsequently fuses with a lysosome or vacuole (in mammals, or yeast and plants, respectively), allowing degradation of the cargo followed by recycling of the resulting macromolecules. Through this basic mechanism, macroautophagy has a critical role in cellular homeostasis; however, either insufficient or excessive macroautophagy can seriously compromise cell physiology, and thus it needs to be properly regulated. In fact, a wide range of diseases is associated with dysregulation of macroautophagy. There has been substantial progress in understanding the regulation and molecular mechanisms of macroautophagy in different organisms; however, many questions concerning some most fundamental aspects of macroautophagy still remain unresolved. In this review, we summarize current knowledge about macroautophagy mainly in yeast, including the mechanism of autophagosome biogenesis, the function of the core macroautophagic machinery, the regulation of macroautophagy, and the process of cargo recognition in selective macroautophagy, with the goal of providing insights into some of the key unanswered questions in this field.

Hepatic cytochromes P450: structural degrons and barcodes, posttranslational modifications and cellular adapters in the ERAD-endgame

“…ALD is a highly conserved eukaryotic process, once thought to involve the bulk degradation of senescent, long-lived proteins/organelles as well as cytosolic components following starvation (Mizushima et al, 2008; Klionsky et al, 2010; Rabinowitz & White, 2010; Cuervo, 2011; Rubinsztein et al, 2012). It is now recognized to be both a rather tightly regulated and selective process entailing macroautophagy with subsequent lysosomal degradation (Mizushima et al, 2008; Yang & Klionsky, 2009; Klionsky et al, 2010; Mizushima et al, 2010; Rabinowitz & White, 2010; Cuervo, 2011; Rubinsztein et al, 2012; Ohsumi, 2014; Madrigal-Matute & Cuervo, 2015; Bento et al, 2016; Wen & Klionsky, 2016). Macroautophagy (or autophagy for short) involves the concerted function of over 35 a u t ophagy-related g enes (ATGs; Mizushima et al, 2008; Yang & Klionsky, 2009; Klionsky et al, 2010; Mizushima et al, 2010; Rabinowitz & White, 2010; Cuervo, 2011; Rubinsztein et al, 2012; Ohsumi, 2014; Madrigal-Matute & Cuervo, 2015; Bento et al, 2016; Wen & Klionsky, 2016) that generate multiprotein complexes that act cooperatively and sequentially to deliver the cargo for lysosomal degradation (Fig.…”

Vps34 Kinase Domain Dynamics Regulate the Autophagic PI 3-Kinase Complex

“…Autophagy thus provides a short-term supply of amino acids in starvation (Wen and Klionsky, 2016). Moreover, autophagy removes aggregated proteins, damaged organelles and intracellular pathogens (Mizushima et al, 2008).…”

BRD4 is a newly characterized transcriptional regulator that represses autophagy and lysosomal function

“…Moreover, successful autophagy requires fusion of autophagosomes with the vacuole in yeast and plants or the lysosome in other eukaryotes for further degradation and recycling. 1 Most of the core machinery of autophagy-those components that play a critical role in autophagosome formation-have been identified with the discovery of over 40 autophagy-related (ATG) genes in yeast; many of which are conserved in more complex eukaryotes. 2,3 However, there are still many questions that remain to be answered with regard to autophagy regulation.…”