Table 1.
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.