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Secreted protein | Protein function | Method(s) used to modulate autophagy | Autophagy’s effect on secretion | Ref. |
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Acb1 | Acyl-CoA-binding protein involved in yeast sporulation | ATG1, 5, 6, 7, 8, 9, 12, 17 and VAM7 mutant yeast; rapamycin | Positive; genetic inhibition of autophagy decreased and rapamycin increased secretion. Fusion of the autophagosome with the vacuole was not related to secretion. | [67, 68] |
Amyloid-β peptide | Element of the amyloid plaques involved in Alzheimer’s disease | Atg7−/− | Positive; genetic inhibition of autophagy caused intracellular Ab accumulation and reduced amyloid B peptide secretion. | [72] |
Annexin A1 | Regulator of the inflammatory process | Beclin1 kd, 3MA, and Atg5−/− | Positive; genetic inhibition of autophagy or 3MA treatment decreased secretion induced by inflammasome activators. Found in screening experiments of secreted proteins regulated by autophagy. | [66, 70, 108] |
Annexin A2 | Ca2+-dependent phospholipid-binding protein | ATG5 kd, 3MA, and lysosomal inhibitors | Positive; genetic inhibition of autophagy or 3MA treatment decreased secretion in IFN-γ-stimulated lung epithelial cells. Found in screening experiments of secreted proteins regulated by autophagy. | [70, 86] |
α-Synuclein | Aggregation-prone protein involved in Parkinson’s disease | ATG5 kd, TPPP/p25 which impaired autophagic flux at the lysosomal fusion step, trehalose, and lysosomal inhibitors | Positive; autophagy inhibition in the presence of TPP/p25 decreased secretion. Autophagosome-lysosome fusion impairment was necessary for secretion, and autophagosome-lysosome fusion impairment enhanced secretion of an LC3/p62+ vesicle. | [69, 70] |
β-Hexosaminidase | Lysosomal enzyme, indicator of mast cell degranulation | Atg7−/− and Atg12 kd | Positive; genetic inhibition of autophagy decreased mast cell degranulation. | [75] |
Cathepsin D | Lysosomal protease | Beclin1 kd, 3MA, and Atg5−/− | Positive; genetic inhibition of autophagy or 3MA treatment decreased secretion induced by inflammasome activators. Found in screening experiments of secreted proteins regulated by autophagy. | [66, 108] |
Cathepsin K | Bone resorption | Atg5−/−, Atg7−/−, and Atg4C74A dominant negative | Positive; autophagy inhibition decreased secretory lysosome delivery to the plasma membrane. | [74] |
CXCL8 | Chemokine produced by macrophages and epithelial cells | ATG7 kd | Positive; autophagy inhibition decreased secretion. | [100] |
DKK3 | Glycoprotein with angiogenesis and invasiveness-promoting roles | ATG7 kd | Positive; autophagy inhibition decreased secretion. | [100] |
FAM3C | Secreted protein inducer of EMT | ATG7 kd | Positive; autophagy inhibition decreased secretion. | [100] |
Ferritin | Iron storage protein | LC3B kd | Positive; inhibition of autophagy decreased secretion in response to lysosomal damage. | [66] |
Galectin 3 | Lectin with affinity for β-galactoside glycoconjugates | Beclin1 kd and 3MA | Positive; genetic inhibition of autophagy or 3MA treatment decreased secretion induced by inflammasome activators. | [108] |
Histamine | Inflammatory response, component of mast cell granules | Atg7−/− and Atg12 kd | Positive; genetic inhibition of autophagy decreased mast cell degranulation. | [75] |
HMGB1 | Alarmin normally present in the nucleus and released during cell death | ATG5, 7, and 12 kd | Positive; genetic inhibition of autophagy decreased secretion in cancer cells treated with targeted therapy. | [93] |
IL-1β | Inflammatory response | Atg5−/−, bafilomycin A [64], beclin 1 kd, 3MA [108], ATG16L1, LC3B kd [66], and Atg7−/− [91] | Positive; genetic [64] or pharmacological [108] inhibition of autophagy decreased secretion in response to inflammasome activation, lysosomal damage [66], or UVB irradiation [91]. | [64, 66, 91, 108] |
Truncated Atg16L1, Atg7−/−, and 3MA [63, 77], Map1lc3b−/− or becn1−/− [76], and becn1 kd [77] | Negative; genetic autophagy inhibition or PI3K inhibitor treatment induced secretion in LPS primed macrophages. | [63, 76, 77] |
IL-6 | Inflammation | ATG5, ATG7, ATG12, beclin1 kd, and Atg7−/− | Positive; genetic inhibition of autophagy decreased secretion in cancer cell lines [40, 57, 89], in UVB irradiated skin [91], or in hepatitis virus infected hepatocytes [109]. | [40, 57, 89, 91, 109] |
ATG7 and Beclin1 kd | Negative; genetic inhibition of autophagy increased secretion in a breast cancer cell line but not others. | [40] |
IL-8 | Chemotactic factor and neutrophil activator | ATG5 and ATG7 kd | Positive; genetic inhibition of autophagy decreased secretion in cancer cell lines [100] or in hepatitis virus-infected hepatocytes [109]. | [100, 109] |
IL-18 | Proinflammatory cytokine | Truncated ATG16L1 [63] and Map1lc3b−/− or Becn1−/− [76] | Negative; genetic autophagy inhibition induced secretion in mouse models of colitis or sepsis or in LPS-primed macrophages. | [63, 76] |
3MA or bafilomycin treatment | Positive; pharmacological inhibition of both initial and degradation phases of autophagy decreased secretion in allergen-induced IL-18 secretion. | [110] |
LIF | Cytokine involved in hematopoietic differentiation, stem cell development, metabolism, and growth promotion | ATG7 kd | Positive; autophagy inhibition decreased secretion. | [100] |
Lysozyme | Antimicrobial protein | Hypomorphic ATG16L1, Atg5−/− [61] and Atg16L1T300A, 3MA, and CQ [62] | Positive; lysozyme secretion was impaired from Paneth cells by genetic inhibition of Atg genes or 3MA but not CQ treatment. | [61, 62] |
Metalloproteinase 2/9 | Extracellular matrix-degrading proteases | ATG7 and 12 kd | Positive; genetic inhibition of autophagy decreased secretion. | [57] |
MIF | Proinflammatory cytokine | Atg5 kd, atg7−/−, and 3MA treatment | Negative; inhibition of autophagy increased MIF secretion in LPS-stimulated macrophages. | [80] |
Neuropeptide Y | Neurotransmitter | Atg16L1 kd | Positive; Atg16L1 kd but not Atg13 or ULK1 kd decreased secretion in neuroendocrine cells. | [111] |
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