Pexophagy: The Selective Degradation of Peroxisomes

Table 1

Genes involved in macro- and micropexophagy in methylotrophic yeasts. Involvement of the respective genes in the different modes of pexophagy is indicated by check marks. Genes denoted in bold font are (by current knowledge) exclusively involved in pexophagy, but not in other autophagy pathways. Genes denoted in regular font represent components of the core machinery involved in different autophagy pathways in the methylotrophic yeasts Pichia pastoris (Pp) and Hansenula polymorpha (Hp). Empty spaces and parentheses depict the current lack of conclusive evidence. Table adapted from Sakai et al. [55].

Gene	Description of molecular events	Macropexophagy		Micropexophagy	Reference
		Pp	Hp	Pp
ATG1	Serine/threonine kinase required for PAS formation	✓	✓	✓	[42, 56, 57]
ATG2	Peripheral membrane protein required for Atg9 recycling	✓		✓	[58]
ATG3	E2-like ubiquitin ligase that catalyzes lipidation of Atg8			✓	[59]
ATG4	Protease that processes Atg8 as prerequisite for conjugation with phosphatidylethanolamine (PE)			✓	[60, 61]
ATG6	Subunit of PI3K complexes I and II	✓			[35]
ATG7	E1-(ubiquitin activating enzyme)-like protein involved in conjugation of Atg12-Atg5 and Atg8-PE conjugates	✓		✓	[42, 62]
ATG8	Ubiquitin-like protein that is anchored to the expanded phagophore membrane in its processed and lipidated form, involved in phagophore membrane expansion	✓	✓	✓	[33, 60, 61]
ATG9	Transmembrane protein cycling between the PAS and a peripheral compartment	✓		✓	[57, 63]
ATG11	Coiled-coil adaptor protein that interacts with the core machinery and known receptors for selective autophagy	✓	✓	✓	[64]
ATG16	Essential component of the Atg12-Atg5-Atg16 complex	(✓)		✓	[42]
ATG17	Scaffold protein that is responsible for PAS organization	✓		✓	[34]
ATG18	PtdIns3P-binding protein whose localization is dependent Atg9 and PtdIns-3P; recruits Atg2 and needed for Atg9 recycling	✓		✓	[65, 66]
ATG21	WD40 protein with phosphoinositide binding domain that is involved in pexophagosome formation		✓		[67]
ATG24	Sorting nexin protein involved in fusion events with the vacuole	✓		✓	[33]
ATG25	Coiled-coil protein that co-localizes with Atg11 at the PAS, required for macropexophagy		✓		[39]
ATG26	Sterol glucosyltransferase that plays a role in phagophore membrane expansion	✓		✓	[44, 46, 68]
ATG28	Coiled-coil protein required for peroxisome sequestration during micropexophagy and vacuole fusion of pexophagosomes in macropexophagy	✓		✓	[69]
ATG30	Pexophagy receptor that interacts with peroxins, Pex3 and Pex14, and adaptor proteins, Atg11 and Atg17	✓		✓	[34]
ATG35	Localizes to the perinuclear structure; regulates MIPA formation and interacts with Atg28 and Atg17			✓	[43]
GCN1-4	Involved in general amino acid control			✓	[42]
Sar1	Sec protein required for MIPA and proper pexophagosome formation		✓	✓	[70]
PEP4	Vacuolar protease			✓	[60]
PEX3	PMP peroxin required for peroxisome biogenesis and for recruitment of pexophagy receptor	✓	✓	✓	[34, 71, 72]
PEX14	PMP peroxin required for peroxisome biogenesis and for recruitment of pexophagy receptor	✓	✓	✓	[34, 73]
PIK1	PtdIns-4-kinase required for MIPA formation			✓	[46]
PFK1	Subunit of phosphofructokinase complex			✓	[62]
TUP1	Transcriptional repressor	✓			[74]
VAC8	N-myristoylated armadillo-repeat protein of the vacuolar membrane, required for VSM formation			✓	[75, 76]
VAM7	SNARE protein that is involved in vacuolar fusion events with the phagophore membrane		✓		[45]
VPS15	Regulatory subunit of PI3K	✓	✓	✓	[42, 77]
VPS34	Phosphatidylinositol-3-kinase (PI3K)	✓	✓	✓	[36, 78]
YPT7	Rab GTPase involved in phagophore membrane fusion	✓	✓	✓	[71, 79]