Origin of the Autophagosome Membrane in Mammals

Table 1

The function of ATG proteins in AP.

ATG Proteins		Features	Function in AP
Mammals	Yeast
ULK1/2 [7]	ATG1	Serine/threonine kinase; form a complex with mATG13, FIP200 and ATG101; phosphorylated by mTORC1 and AMPK kinases	late stage of AP biogenesis
ATG2A/B [8]	ATG2	Interacts with ATG18; associates to autophagosomal membranes through lipid binding and independently from ATG9	closure of the AP membrane, late stage of AP biogenesis
ATG3[9]	ATG3	E2-like enzyme	facilitates LC3/GABARAP lipidation in highly curved membranes; curvature and maturation of AP biogenesis
ATG4A-D [1]	ATG4	cysteine protease; phosphorylation by ATG1	initial stage of phagophore formation
ATG5[10]	ATG5	conjugated by ATG12	elongation of the isolation membranes, the AP-formation marker
Beclin1	ATG6,; vacuolar protein sorting (Vps)-30	conjugated by PI3KC3 and ULK	intervene at every major step in autophagic pathways, from autophagosome formation, to autophagosome/endosome maturation
ATG7	ATG7	autophagy-related E1-like enzyme	elongation of the AP membranes
LC3A/B/C, GABARAP, GATE-16, GABARAPL1/2/3 [4]	ATG8	ubiquitin-like protein; conjugates to phosphatidylethanolamine (PE)	determines the size of AP; induce membrane tethering and fusion; expansion and closure of phagophores
ATG9L1 [11]	ATG9	transmembrane autophagy-related protein	initial stage of AP formation, generate the isolation membrane
ATG10	ATG10	E2-like enzyme; catalyze or facilitate ATG5-12 conjugation	promotes autophagolysosome formation
—	ATG11	Scaffold Protein	regulates autophagosome-vacuole fusion
ATG12 [12]	ATG12	ubiquitin-like molecules; conjugates to ATG5	elongation and maturation of the phagophore membrane
KIAA0652; [13]	ATG13	Phosphorylated by (m)TORC1	later stage of autophagosome maturation
ATG14(L)/Barkor [14]	ATG14	autophagy-specific subunit	fusion of APs to endolysosomes, regulates autophagosome nucleation; the preautophagosome/autophagosome marker
ATG16L1/2 [15]	ATG16	conjugated by ATG12 and ATG5, E3‐Ubiquitin ligase‐like enzyme	elongation of AP membrane
WIPI1/2/3/4 [16]	ATG18	PtdIns(3)P-binding protein	recycle of membrane proteins from the vacuole to the late endosome
ATG19 [17]	ATG19	contains multiple ATG8 binding sites	serves as cargo receptor and directly interacts with ATG8 on the isolation membrane
—	ATG20 [18]	sorting nexin	required for efficient autophagy and membrane tubulation
—	ATG21	PtdIns(3)P-binding protein, only detected at endosomes	facilitates the recruitment of Atg8-PE to the site of autophagosome formation
_	ATG23	peripheral membrane protein	facilitates Atg9 trafficking
SNX4	ATG24 [19]	a member of the BAR domain family of proteins	inhibits the number of APs
—	ATG27 [20]	transmembrane protein	retrieval of Atg9 from the vacuole
RB1CC1/FIP200	ATG17	PI3P binding effector
—	ATG29	Ternary complex with Atg17 and Atg31	Atg29-Atg31-Atg17 complex [21], formation a dimer with two crescents for fusion into the expanding phagophore
—	ATG31	Ternary complex with Atg17 and Atg29
—	ATG32 [22]	outer mitochondrial membrane protein	essential for the initiation of mitophagy; facilitates mitochondrial capture in phagophores
ATG101	—	Interacts with Atg13; maintains ULK1 basal phosphorylation	interacts with the ULK1 complex via direct binding to ATG13 to induce the formation of AP