Autophagy and Its Lineage-Specific Roles in the Hematopoietic System

Table 1

Canonical autophagy-dependent and canonical autophagy-independent function(s) of different autophagy marker proteins.

Protein name	Autophagy step(s)	Canonical autophagy-dependent function(s)	Rf.	Canonical autophagy-independent function(s)	Rf.
ULK1 or ATG1	Initiation	Mitochondrial respiration, ATP production, lipid metabolism, and mitochondrial and ribosomal clearance	[97, 98]	Cell death and apoptosis, endocytosis, immune signaling, antiproliferative and antineoplastic effects in MPNs, ER-to-Golgi trafficking, cellular homeostasis, ammonia-induced autophagy, and endosomal trafficking	[99–106]
ATG2A or ATG2B	Elongation	Regulates lipid homeostasis, promotes Atg9-Atg18 interaction, and programmed cell size reduction	[107–109]	iDISC-dependent caspase-8 activation, apoptosis, and lipid droplet localization	[110, 111]
ATG3	Elongation	Induces HIV infection and cell death	[112]	LAP, endosomal trafficking, and apoptosis	[74, 113, 114]
ATG4B or ATG4D	Elongation	Sense balance and otoconial development induce HIV infection and cell death	[112, 115]	LAP, mitochondrial dysfunction, and apoptosis	[74, 116]
ATG5	Elongation	Maintenance of innate lymphocytes, skeletal homeostasis, and antiviral immune responses	[117–119]	Immunity, intracellular pathogen killing, apoptosis, and adipogenesis	[120–123]
ATG6 or Beclin1	Nucleation	Induces HIV infection and cell death	[112]	Apoptosis, cell death, cancer cell growth, embryogenesis, tumor suppression, STAT3 phosphorylation, DNA damage repair, receptor degradation, and cytokinesis and induces viral transmission and improves the life span	[124–132]
ATG7	Elongation	Maintains cellular and behavioral responses and regulates potassium (K^+) level in hypokalemia	[133, 134]	Cell shrinkage, cell cycle arrest, mitochondrial clearance, adipogenesis, and ISC integrity maintenance and promotes neuronal health and longevity	[109, 121, 135–137]
ATG8 or LC3	Cargo selection	Maintains tissue homeostasis	[138]	LAP, apoptosis, virus replication, cancer cell survival, lysosome biogenesis, and exocytosis	[68, 120, 139–141]
ATG9	Initiation	Pathogenesis of POI	[142]	Maintains lysosomal degradation, axonal degeneration, STING, and TBK1 assembly	[143, 144]
ATG10	Elongation	Not known	-	Apoptosis, deficiency leads to ALS and FTD molecular defects, lysosomal degradation, and suppression of HCV replication	[145–147]
ATG12	Elongation	Mitochondrial homeostasis, cell death, antiviral immune responses, osteoclast secretion, and pathogen control	[119, 148, 149]	Endosomal trafficking, mitochondrial apoptosis, and endosome to lysosome trafficking	[74, 150, 151]
ATG13	Initiation	Cell cycle progression	[152]	Control virus replication and; cardiac development	[153, 154]
ATG14	Nucleation	Autophagosome–endolysosome fusion	[155]	Autophagic cell death	[156]
ATG16l1	Elongation	Urothelial vesicle trafficking	[157, 158]	Apoptosis	[120, 159]
ATG18	Elongation	Programmed cell size reduction	[109]	Neural homeostasis	[160]
ATG101	Initiation	Maintaining respiratory function	[161]	Not known	-
FIP200	Initiation	Maintaining respiratory function	[161]	Control virus replication	[153]
VPS15	Nucleation	Not known	-	Skeletal muscle function, endocytosis, and neuronal migration	[130, 162, 163]
VPS34	Nucleation	T-cell homeostasis	[164]	Endocytosis, receptor degradation, and cytokinesis	[130]

LAP: LC3-associated phagocytosis; iDISC: intracellular death-inducing signaling complex; Rf: reference(s); PAS: preautophagosomal structure; ISC: intestinal stem cell; STING: stimulator of IFN genes; TBK1: TANK-binding kinase 1; POI: primary ovarian insufficiency; FTD: frontotemporal dementia; ALS: amyotrophic lateral sclerosis; HCV: hepatitis C virus; VPS34: vacuolar protein sorting 34.