Mechanistic insights into selective autophagy pathways: lessons from yeast

Abstract

Autophagy has burgeoned rapidly as a field of study because of its evolutionary conservation, the diversity of intracellular cargoes degraded and recycled by this machinery the mechanisms involved, as well as its physiological relevance to human health and disease. This self-eating process was initially viewed as a non-selective mechanism used by eukaryotic cells to degrade and recycle macromolecules in response to stress; we now know that various cellular constituents, as well as pathogens, can also undergo selective autophagy. In contrast to non-selective autophagy, selective autophagy pathways rely on a plethora of selective autophagy receptors (SARs) that recognize and direct intracellular protein aggregates, organelles and pathogens for specific degradation. Although SARs themselves are not highly conserved, their modes of action and the signalling cascades that activate and regulate them are. Recent yeast studies have provided novel mechanistic insights into selective autophagy pathways, revealing principles of how various cargoes can be marked and targeted for selective degradation.

Limited and digestive proteolysis: crosstalk between evolutionary conserved pathways

“…Similarly, a typical inducer of bulk autophagy in yeast cells, nitrogen starvation, stimulates preferential degradation of the acetaldehyde dehydrogenase ALd6P, whose enzymatic activity would otherwise reduce cell viability under such conditions (Onodera & Ohsumi, 2004). A growing number of discovered receptors/adaptors for selective autophagy points to the complexity of autophagy selectivity, which originally might have been viewed as lacking selectivity (Dengjel et al, 2012;Mancias et al, 2014;Farre & Subramani, 2016), and also indicates that selectivity of autophagy is most probably determined at the cargo recruitment stage.…”

Dengue and Zika viruses subvert reticulophagy by NS2B3-mediated cleavage of FAM134B

“…15 A number of other forms of selective autophagy have been described including degradation of ribosomes (ribophagy), peroxisomes (pexophagy), mitochondria (mitophagy), and ER (reticulophagy). 23 However, the molecular mechanisms that regulate many of these processes have not been well characterized for mammalian cells and, thus, have not been investigated during viral infection.…”

Transcriptional and post-transcriptional regulation of autophagy in the yeast Saccharomyces cerevisiae

“…In particular, of the ATG transcripts that were examined in this study, dhh1Δ cells demonstrated significantly increased levels of ATG3, 7,8,19,20,22 and 24 mRNA under nutrient-replete conditions (96). In the dcp2-7Δ ts strain, transcript levels for ATG1 through ATG9, ATG11, ATG13 through ATG24, ATG29, 31, 32 and 34 were significantly upregulated in rich conditions (96).…”

“…At least in yeast, the receptors utilized to target cargos are unique to the form of selective autophagy that the cell is undergoing (5,7,8,21). For further discussion on the topic of selective autophagy, see refs, (22,23).…”

“…ATG3, 7,8,19,20,22,11,[13][14][15][16][17][18][19][20][21][22][23][24]29,31,32,34 TORC1 ATG1, 4,5,7,8,12,14,16,29,31 X r n 1 …”