RECENT ADVANCES IN AUTOPHAGY AND VESICLE TRAFFICKING IN PANCREATIC DISEASES: MOLECULAR MECHANISMS AND SELECTIVE AUTOPHAGY PATHWAYS
DOI:
https://doi.org/10.31435/ijitss.3(51).2026.6327Keywords:
Autophagy; Pancreas; Vesicle Trafficking; Selective Autophagy; Cellular Homeostasis; Pancreatitis; Pancreatic CancerAbstract
Autophagy is a key lysosome-dependent degradation pathway essential for maintaining cellular homeostasis, particularly in the highly secretory pancreas. This review summarizes recent advances in autophagy, selective autophagy, and vesicle trafficking in pancreatic physiology and disease. We focus on the dual role of autophagy, which can support cellular protection and organelle quality control, but also contribute to pathology when dysregulated. We highlight emerging molecular mechanisms linking autophagy with vesicle trafficking systems, including membrane remodeling, organelle contact sites, and key regulators such as VMP1 and Beclin-1. In addition, we discuss the role of autophagy in pancreatic inflammation and cancer, emphasizing its context-dependent function. Finally, we outline recent translational approaches targeting autophagy-related pathways, including pharmacological and genetic strategies, with potential diagnostic and therapeutic relevance in pancreatic diseases.
References
Li, J., Chen, X., Kang, R., Zeh, H., Klionsky, D. J., & Tang, D. (2021). Regulation and function of autophagy in pancreatic cancer. Autophagy, 17(11), 3275–3296. https://doi.org/10.1080/15548627.2020.1847462
Siegel, R. L., Miller, K. D., & Jemal, A. (2019). Cancer statistics, 2019. CA: A Cancer Journal for Clinicians, 69(1), 7–34. https://doi.org/10.3322/caac.21551
Levy, J. M. M., Towers, C. G., & Thorburn, A. (2017). Targeting autophagy in cancer. Nature Reviews Cancer, 17(9), 528–542. https://doi.org/10.1038/nrc.2017.53
Ozaki, N., Fukuchi, Y., Tomiyoshi, S. R., Uehara, H., Ida, S., Wang, J., Araki, K., Sibilia, M., Baba, H., Yamamura, K., & Ohmuraya, M. (2014). Autophagy regulation in pancreatic acinar cells is independent of epidermal growth factor receptor signaling. Biochemical and Biophysical Research Communications, 446(1), 224–230. https://doi.org/10.1016/j.bbrc.2014.02.111
Amiri, B. S., Naserranjbar, M., Aliabadi, F., Hejrati, A., & Hejrati, L. (2025). Autophagy: A novel target in order to overcome drug resistance in pancreatic adenocarcinoma. Open Biology, 15(10), 240412. https://doi.org/10.1098/rsob.240412
Nagelkerke, A., Sweep, F. C., Geurts-Moespot, A., Bussink, J., & Span, P. N. (2015). Therapeutic targeting of autophagy in cancer. Part I: Molecular pathways controlling autophagy. Seminars in Cancer Biology, 31, 89–98. https://doi.org/10.1016/j.semcancer.2014.05.004
Dalby, K. N., Tekedereli, I., Lopez-Berestein, G., & Ozpolat, B. (2010). Targeting the prodeath and prosurvival functions of autophagy as novel therapeutic strategies in cancer. Autophagy, 6(3), 322–329. https://doi.org/10.4161/auto.6.3.11625
Liu, T., Zhang, J., Li, K., Deng, L., & Wang, H. (2020). Combination of an autophagy inducer and an autophagy inhibitor: A smarter strategy emerging in cancer therapy. Frontiers in Pharmacology, 11, 408. https://doi.org/10.3389/fphar.2020.00408
Amiri, B. S., Naserranjbar, M., Aliabadi, F., Hejrati, A., & Hejrati, L. (2025). Autophagy: A novel target in order to overcome drug resistance in pancreatic adenocarcinoma. Open Biology, 15(10), 240412. https://doi.org/10.1098/rsob.240412
Kuo, C. J., Hansen, M., & Troemel, E. (2018). Autophagy and innate immunity: Insights from invertebrate model organisms. Autophagy, 14(2), 233–242. https://doi.org/10.1080/15548627.2017.1389824
Yang, S., Wang, X., Contino, G., Liesa, M., Sahin, E., Ying, H., Bause, A., Li, Y., Stommel, J. M., Dell’Antonio, G., Mautner, J., Tonon, G., Haigis, M., Shirihai, O. S., Doglioni, C., Bardeesy, N., & Kimmelman, A. C. (2011). Pancreatic cancers require autophagy for tumor growth. Genes & Development, 25(7), 717–729. https://doi.org/10.1101/gad.2016111
Maertin, S., Elperin, J. M., Lotshaw, E., Sendler, M., Speakman, S. D., Takakura, K., Reicher, B. M., Mareninova, O. A., Grippo, P. J., Mayerle, J., Lerch, M. M., & Gukovskaya, A. S. (2017). Roles of autophagy and metabolism in pancreatic cancer cell adaptation to environmental challenges. American Journal of Physiology-Gastrointestinal and Liver Physiology, 313(5), G524–G536. https://doi.org/10.1152/ajpgi.00138.2017
Gukovskaya, A. S., Gukovsky, I., Algül, H., & Habtezion, A. (2017). Autophagy, inflammation, and immune dysfunction in the pathogenesis of pancreatitis. Gastroenterology, 153(5), 1212–1226. https://doi.org/10.1053/j.gastro.2017.08.071
Antonucci, L., Fagman, J. B., Kim, J. Y., Todoric, J., Gukovsky, I., Mackey, M., Ellisman, M. H., & Karin, M. (2015). Basal autophagy maintains pancreatic acinar cell homeostasis and protein synthesis and prevents ER stress. Proceedings of the National Academy of Sciences of the United States of America, 112(45), E6166–E6174. https://doi.org/10.1073/pnas.1519384112
Yang, Z., & Klionsky, D. J. (2010). Mammalian autophagy: Core molecular machinery and signaling regulation. Current Opinion in Cell Biology, 22(2), 124–131. https://doi.org/10.1016/j.ceb.2009.11.014
Parzych, K. R., & Klionsky, D. J. (2014). An overview of autophagy: Morphology, mechanism, and regulation. Antioxidants & Redox Signaling, 20(3), 460–473. https://doi.org/10.1089/ars.2013.5371
Jahn, R., & Scheller, R. H. (2006). SNAREs—Engines for membrane fusion. Nature Reviews Molecular Cell Biology, 7(9), 631–643. https://doi.org/10.1038/nrm2002
Cohen, S., Valm, A. M., & Lippincott-Schwartz, J. (2018). Interacting organelles. Current Opinion in Cell Biology, 53, 84–91. https://doi.org/10.1016/j.ceb.2018.06.003
Cui, L., Li, H., Xi, Y., Hu, Q., Liu, H., Fan, J., Xiang, Y., Zhang, X., Shui, W., & Lai, Y. (2022). Vesicle trafficking and vesicle fusion: Mechanisms, biological functions, and their implications for potential disease therapy. Molecular Biomedicine, 3(1), 29. https://doi.org/10.1186/s43556-022-00090-3
Ramachandran, S., Kaushik, I. S., & Srivastava, S. K. (2021). Pimavanserin: A novel autophagy modulator for pancreatic cancer treatment. Cancers, 13(22), 5661. https://doi.org/10.3390/cancers13225661
Hinzman, C. P., Singh, B., Bansal, S., Li, Y., Iliuk, A., Girgis, M., Herremans, K. M., Trevino, J. G., Singh, V. K., Banerjee, P. P., & Cheema, A. K. (2022). A multi-omics approach identifies pancreatic cancer cell extracellular vesicles as mediators of the unfolded protein response in normal pancreatic epithelial cells. Journal of Extracellular Vesicles, 11(6), e12232. https://doi.org/10.1002/jev2.12232
Zhou, Z., Zhang, P., Li, J., Yao, J., Jiang, Y., Wan, M., Tang, W., & Liu, L. (2024). Autophagy and the pancreas: Healthy and disease states. Frontiers in Cell and Developmental Biology, 12, 1460616. https://doi.org/10.3389/fcell.2024.1460616
Yazıcı, Ö., Kara, M., Boran, T., & Ozhan, G. (2023). The role of endoplasmic reticulum stress in cell injury induced by methimazole on pancreatic cells. Advanced Pharmaceutical Bulletin, 13, 196–201. https://doi.org/10.34172/apb.2023.042
Pérez, S., Pereda, J., Sabater, L., & Sastre, J. (2015). Redox signaling in acute pancreatitis. Redox Biology, 5, 1–14. https://doi.org/10.1016/j.redox.2015.01.014
Xia, L., Xu, Z., Zhou, X., Bergmann, F., Grabe, N., Büchler, M. W., et al. (2020). Impaired autophagy increases susceptibility to endotoxin-induced chronic pancreatitis. Cell Death & Disease, 11, 889. https://doi.org/10.1038/s41419-020-03050-3
Smith, M. D., Harley, M. E., Kemp, A. J., Wills, J., Lee, M., Arends, M., et al. (2018). CCPG1 is a non-canonical autophagy cargo receptor essential for ER-phagy and pancreatic ER proteostasis. Developmental Cell, 44, 217–232. https://doi.org/10.1016/j.devcel.2017.11.024
Smith, M. D., & Wilkinson, S. (2018). CCPG1, a cargo receptor required for reticulophagy and endoplasmic reticulum proteostasis. Autophagy, 14(6), 1090–1091. https://doi.org/10.1080/15548627.2018.1441473
Sudhakar, J. N., Lu, H. H., Chiang, H. Y., Suen, C. S., Hwang, M. J., Wu, S. Y., et al. (2020). Lumenal Galectin-9-Lamp2 interaction regulates lysosome and autophagy to prevent pathogenesis in the intestine and pancreas. Nature Communications, 11, 4286. https://doi.org/10.1038/s41467-020-18102-7
Wang, Q., Yu, J., Gao, W., Sun, Y., Liu, X., Lv, Z., et al. (2022). The lncRNA TCONS_00021785/miR-21-5p/Trim33 axis regulates VMP1-mediated zymophagy, reduces the activation of trypsinogen, and promotes acinar cell recovery. Cell Death Discovery, 8, 65. https://doi.org/10.1038/s41420-022-00862-4
Vaccaro, M. I., Ropolo, A., Grasso, D., & Iovanna, J. L. (2008). A novel mammalian trans-membrane protein reveals an alternative initiation pathway for autophagy. Autophagy, 4, 388–390. https://doi.org/10.4161/auto.5656
Grasso, D., Sacchetti, M. L., Bruno, L., Lo Ré, A., Iovanna, J. L., Gonzalez, C. D., et al. (2009). Autophagy and VMP1 expression are early cellular events in experimental diabetes. Pancreatology, 9, 81–88. https://doi.org/10.1159/000178878
Dolai, S., Liang, T., Orabi, A. I., Xie, L., Holmyard, D., Javed, T. A., et al. (2018). Depletion of the membrane-fusion regulator Munc18c attenuates caerulein hyperstimulation-induced pancreatitis. Journal of Biological Chemistry, 293, 2510–2522. https://doi.org/10.1074/jbc.RA117.000792
Iwahashi, K., Hikita, H., Makino, Y., Shigekawa, M., Ikezawa, K., Yoshioka, T., et al. (2018). Autophagy impairment in pancreatic acinar cells causes zymogen granule accumulation and pancreatitis. Biochemical and Biophysical Research Communications, 503, 2576–2582. https://doi.org/10.1016/j.bbrc.2018.07.018
Ebato, C., Uchida, T., Arakawa, M., Komatsu, M., Ueno, T., Komiya, K., et al. (2008). Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet. Cell Metabolism, 8, 325–332. https://doi.org/10.1016/j.cmet.2008.08.009
Gurlo, T., Kim, S., Butler, A. E., Liu, C., Pei, L., Rosenberger, M., et al. (2019). Pregnancy in human IAPP transgenic mice recapitulates beta cell stress in type 2 diabetes. Diabetologia, 62, 1000–1010. https://doi.org/10.1007/s00125-019-4843-z
Hwang, W. M., Bak, D. H., Kim, D. H., Hong, J. Y., Han, S. Y., Park, K. Y., et al. (2015). Omega-3 polyunsaturated fatty acids may attenuate streptozotocin-induced pancreatic β-cell death via autophagy activation in Fat1 transgenic mice. Endocrinology and Metabolism, 30, 569–575. https://doi.org/10.3803/EnM.2015.30.4.569
Saluja, A., Dudeja, V., Dawra, R., & Sah, R. P. (2019). Early intra-acinar events in pathogenesis of pancreatitis. Gastroenterology, 156, 1979–1993. https://doi.org/10.1053/j.gastro.2019.01.268
Mareninova, O. A., Jia, W., Gretler, S. R., Holthaus, C. L., Thomas, D. D. H., Pimienta, M., et al. (2020). Transgenic expression of GFP-LC3 perturbs autophagy in exocrine pancreas and acute pancreatitis responses in mice. Autophagy, 16, 2084–2097. https://doi.org/10.1080/15548627.2020.1715047
Dolai, S., Takahashi, T., Qin, T., Liang, T., Xie, L., Kang, F., et al. (2021). Pancreas-specific SNAP23 depletion prevents pancreatitis by attenuating pathological basolateral exocytosis and formation of trypsin-activating autolysosomes. Autophagy, 17, 1–14. https://doi.org/10.1080/15548627.2020.1852725
Dolai, S., Liang, T., Orabi, A. I., Xie, L., Holmyard, D., Javed, T. A., et al. (2018). Depletion of the membrane-fusion regulator Munc18c attenuates caerulein hyperstimulation-induced pancreatitis. Journal of Biological Chemistry, 293, 2510–2522. https://doi.org/10.1074/jbc.RA117.000792
Iovanna, J. L. (2017). Autophagy contributes to the initiation of pancreatic cancer. Médecine/Sciences, 33, 335–339. https://doi.org/10.1051/medsci/20173303022
Gong, J., Belinsky, G., Sagheer, U., Zhang, X., Grippo, P. J., & Chung, C. (2016). Pigment epithelium-derived factor (PEDF) blocks Wnt3a protein-induced autophagy in pancreatic intraepithelial neoplasms. Journal of Biological Chemistry, 291, 22074–22085. https://doi.org/10.1074/jbc.M116.729962
Todoric, J., Antonucci, L., Di Caro, G., Li, N., Wu, X., Lytle, N. K., et al. (2017). Stress-activated NRF2-MDM2 cascade controls neoplastic progression in pancreas. Cancer Cell, 32, 824–839. https://doi.org/10.1016/j.ccell.2017.10.011
Vargas, J. N. S., Hamasaki, M., Kawabata, T., Youle, R. J., & Yoshimori, T. (2023). The mechanisms and roles of selective autophagy in mammals. Nature Reviews Molecular Cell Biology, 24(3), 167–185. https://doi.org/10.1038/s41580-022-00542-2
Kumar, A. V., Mills, J., & Lapierre, L. R. (2022). Selective autophagy receptor p62/SQSTM1, a pivotal player in stress and aging. Frontiers in Cell and Developmental Biology, 10, 793328. https://doi.org/10.3389/fcell.2022.793328
Germain, K., So, R. W. L., DiGiovanni, L. F., Watts, J. C., Bandsma, R. H. J., & Kim, P. K. (2024). Upregulated pexophagy limits the capacity of selective autophagy. Nature Communications, 15(1), 375. https://doi.org/10.1038/s41467-023-44005-4
Zhao, Q., Lin, Y., Han, Z., Tian, Y., Yang, Y., Gou, Q., Ju, Y., Xu, D., & Wei, L. (2026). Autophagy in ocular diseases: From mechanisms to therapeutic potential. Frontiers in Cell and Developmental Biology, 14, 1727005. https://doi.org/10.3389/fcell.2026.1727005
Bharath, L. P., Rockhold, J. D., & Conway, R. (2021). Selective autophagy in hyperglycemia-induced microvascular and macrovascular diseases. Cells, 10(8), 2114. https://doi.org/10.3390/cells10082114
Vaccaro, M. I., Mitchell, F., Rivera, F., & Gonzalez, C. D. (2022). Protein expression in exocrine pancreatic diseases. Focus on VMP1 mediated autophagy. Advances in Protein Chemistry and Structural Biology, 132, 175–197. https://doi.org/10.1016/bs.apcsb.2022.07.001
Vaccaro, M. I. (2012). Zymophagy: Selective autophagy of secretory granules. International Journal of Cell Biology, 2012, 396705. https://doi.org/10.1155/2012/396705
Dusetti, N. J., Jiang, Y., Vaccaro, M. I., Tomasini, R., Azizi Samir, A., Calvo, E. L., Ropolo, A., Fiedler, F., Mallo, G. V., Dagorn, J. C., & Iovanna, J. L. (2002). Cloning and expression of the rat vacuole membrane protein 1 (VMP1), a new gene activated in pancreas with acute pancreatitis, which promotes vacuole formation. Biochemical and Biophysical Research Communications, 290(2), 641–649. https://doi.org/10.1006/bbrc.2001.6244
Grasso, D., Ropolo, A., Lo Ré, A., Boggio, V., Molejón, M. I., Iovanna, J. L., Gonzalez, C. D., Urrutia, R., & Vaccaro, M. I. (2011). Zymophagy, a novel selective autophagy pathway mediated by VMP1-USP9x-p62, prevents pancreatic cell death. Journal of Biological Chemistry, 286(10), 8308–8324. https://doi.org/10.1074/jbc.M110.197301
Wang, S., Ni, H. M., Chao, X., Ma, X., Kolodecik, T., De Lisle, R., et al. (2020). Critical role of TFEB-mediated lysosomal biogenesis in alcohol-induced pancreatitis in mice and humans. Cellular and Molecular Gastroenterology and Hepatology, 10, 59–81. https://doi.org/10.1016/j.jcmgh.2020.01.008
Chediack, J. G., Funes, S. C., Cid, F. D., Filippa, V., & Caviedes-Vidal, E. (2012). Effect of fasting on the structure and function of the gastrointestinal tract of house sparrows (Passer domesticus). Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 163, 103–110. https://doi.org/10.1016/j.cbpa.2012.05.189
Yoo, H. S., Moss, K. O., Cockrum, M. A., Woo, W., & Napoli, J. L. (2023). Energy status regulates levels of the RAR/RXR ligand 9-cis-retinoic acid in mammalian tissues: Glucose reduces its synthesis in β-cells. Journal of Biological Chemistry, 299, 105255. https://doi.org/10.1016/j.jbc.2023.105255
Yang, M., Zhang, D., Li, Y., & Xin, Y. (2020). Maternal protein restriction increases autophagy in the pancreas of newborn rats. Journal of Nutritional Science and Vitaminology, 66, 168–175. https://doi.org/10.3177/jnsv.66.168
Wu, J., Gu, X., Zhang, J., Mi, Z., He, Z., Dong, Y., et al. (2022). 4-OI protects MIN6 cells from oxidative stress injury by reducing LDHA-mediated ROS generation. Biomolecules, 12, 1236. https://doi.org/10.3390/biom12091236
Mareninova, O. A., Sendler, M., Malla, S. R., Yakubov, I., French, S. W., Tokhtaeva, E., et al. (2015). Lysosome associated membrane proteins maintain pancreatic acinar cell homeostasis: LAMP-2 deficient mice develop pancreatitis. Cellular and Molecular Gastroenterology and Hepatology, 1, 678–694. https://doi.org/10.1016/j.jcmgh.2015.07.006
Sudhakar, J. N., Lu, H. H., Chiang, H. Y., Suen, C. S., Hwang, M. J., Wu, S. Y., et al. (2020). Lumenal Galectin-9-Lamp2 interaction regulates lysosome and autophagy to prevent pathogenesis in the intestine and pancreas. Nature Communications, 11, 4286. https://doi.org/10.1038/s41467-020-18102-7
Zhu, H., Bhatt, B., Sivaprakasam, S., Cai, Y., Liu, S., Kodeboyina, S. K., et al. (2019). Ufbp1 promotes plasma cell development and ER expansion by modulating distinct branches of UPR. Nature Communications, 10, 1084. https://doi.org/10.1038/s41467-019-08908-5
Smith, M. D., & Wilkinson, S. (2018a). CCPG1, a cargo receptor required for reticulophagy and endoplasmic reticulum proteostasis. Autophagy, 14, 1090–1091. https://doi.org/10.1080/15548627.2018.1441473
Smith, M. D., & Wilkinson, S. (2018b). CCPG1, an unconventional cargo receptor for ER-phagy, maintains pancreatic acinar cell health. Molecular & Cellular Oncology, 5, e1441631. https://doi.org/10.1080/23723556.2018.1441631
Smith, M. D., Harley, M. E., Kemp, A. J., Wills, J., Lee, M., Arends, M., et al. (2018). CCPG1 is a non-canonical autophagy cargo receptor essential for ER-phagy and pancreatic ER proteostasis. Developmental Cell, 44, 217–232. https://doi.org/10.1016/j.devcel.2017.11.024
Zhao, Y., Feng, X., Li, B., Sha, J., Wang, C., Yang, T., Cui, H., & Fan, H. (2020). Dexmedetomidine protects against lipopolysaccharide-induced acute kidney injury by enhancing autophagy through inhibition of the PI3K/AKT/mTOR pathway. Frontiers in Pharmacology, 11, 128. https://doi.org/10.3389/fphar.2020.00128
Padman, B. S., Nguyen, T. N., Uoselis, L., Skulsuppaisarn, M., Nguyen, L. K., & Lazarou, M. (2019). LC3/GABARAPs drive ubiquitin-independent recruitment of Optineurin and NDP52 to amplify mitophagy. Nature Communications, 10, 408. https://doi.org/10.1038/s41467-019-08335-6
Xia, L., Xu, Z., Zhou, X., Bergmann, F., Grabe, N., Büchler, M. W., et al. (2020). Impaired autophagy increases susceptibility to endotoxin-induced chronic pancreatitis. Cell Death & Disease, 11, 889. https://doi.org/10.1038/s41419-020-03050-3
Kuo, C. J., Hansen, M., & Troemel, E. (2018). Autophagy and innate immunity: Insights from invertebrate model organisms. Autophagy, 14(2), 233–242. https://doi.org/10.1080/15548627.2017.1389824
Iovanna, J. L. (2017). Autophagy contributes to the initiation of pancreatic cancer. Médecine/Sciences, 33, 335–339. https://doi.org/10.1051/medsci/20173303022
Molejon, M. I., Ropolo, A., & Vaccaro, M. I. (2013). VMP1 is a new player in the regulation of the autophagy-specific phosphatidylinositol 3-kinase complex activation. Autophagy, 9(6), 933–935. https://doi.org/10.4161/auto.24390
Zhao, Y. G., Chen, Y., Miao, G., Zhao, H., Qu, W., Li, D., Wang, Z., Liu, N., Li, L., Chen, S., Liu, P., Feng, D., & Zhang, H. (2017). The ER-localized transmembrane protein EPG-3/VMP1 regulates SERCA activity to control ER-isolation membrane contacts for autophagosome formation. Molecular Cell, 67(6), 974–989.e6. https://doi.org/10.1016/j.molcel.2017.08.005
Calvo-Garrido, J., King, J. S., Muñoz-Braceras, S., & Escalante, R. (2014). Vmp1 regulates PtdIns3P signaling during autophagosome formation in Dictyostelium discoideum. Traffic, 15(11), 1235–1246. https://doi.org/10.1111/tra.12210
Wang, P., Chen, X., Wang, Y., Jia, C., Liu, X., Wang, Y., Wu, H., Cai, H., Shen, H. M., & Le, W. (2021). Essential role for autophagy protein VMP1 in maintaining neuronal homeostasis and preventing axonal degeneration. Cell Death & Disease, 12(1), 116. https://doi.org/10.1038/s41419-021-03412-5
Wang, P., Kou, D., & Le, W. (2020). Roles of VMP1 in autophagy and ER-membrane contact: Potential implications in neurodegenerative disorders. Frontiers in Molecular Neuroscience, 13, 42. https://doi.org/10.3389/fnmol.2020.00042
Mizushima, N., & Levine, B. (2020). Autophagy in human diseases. The New England Journal of Medicine, 383(16), 1564–1576. https://doi.org/10.1056/NEJMra2022774
Ge, L., Wilz, L., & Schekman, R. (2015). Biogenesis of autophagosomal precursors for LC3 lipidation from the ER-Golgi intermediate compartment. Autophagy, 11(12), 2372–2374. https://doi.org/10.1080/15548627.2015.1105422
Brier, L. W., Ge, L., Stjepanovic, G., Thelen, A. M., Hurley, J. H., & Schekman, R. (2019). Regulation of LC3 lipidation by the autophagy-specific class III phosphatidylinositol-3 kinase complex. Molecular Biology of the Cell, 30(9), 1098–1107. https://doi.org/10.1091/mbc.E18-11-0743
Amaravadi, R. K., Kimmelman, A. C., & Debnath, J. (2019). Targeting autophagy in cancer: Recent advances and future directions. Cancer Discovery, 9(9), 1167–1181. https://doi.org/10.1158/2159-8290.CD-19-0292
Lamb, C. A., Yoshimori, T., & Tooze, S. A. (2013). The autophagosome: Origins unknown, biogenesis complex. Nature Reviews Molecular Cell Biology, 14(12), 759–774. https://doi.org/10.1038/nrm3696
Nascimbeni, A. C., Giordano, F., Dupont, N., Grasso, D., Vaccaro, M. I., Codogno, P., & Morel, E. (2017). ER-plasma membrane contact sites contribute to autophagosome biogenesis by regulation of local PI3P synthesis. The EMBO Journal, 36(14), 2018–2033. https://doi.org/10.15252/embj.201797006
Zhang, W. G., Wu, Q. Z., & Shao, B. Z. (2024). The role of autophagy in pancreatic diseases. Frontiers in Pharmacology, 15, 1444657. https://doi.org/10.3389/fphar.2024.1444657
Zhu, L., Xu, Y., & Lei, J. (2024). Molecular mechanism and potential role of mitophagy in acute pancreatitis. Molecular Medicine, 30(1), 136. https://doi.org/10.1186/s10020-024-00903-x
Ferretti, G. D. S., Quaas, C. E., Bertolini, I., Zuccotti, A., Saatci, O., Kashatus, J. A., Sharmin, S., Lu, D. Y., Poli, A. N. R., Quesnelle, A. F., Rodriguez-Blanco, J., de Cubas, A. A., Hobbs, G. A., Liu, Q., O’Bryan, J. P., Salvino, J. M., Kashatus, D. F., Sahin, O., & Barnoud, T. (2024). HSP70-mediated mitochondrial dynamics and autophagy represent a novel vulnerability in pancreatic cancer. Cell Death & Differentiation, 31(7), 881–896. https://doi.org/10.1038/s41418-024-01310-9
Gukovskaya, A. S., & Gukovsky, I. (2012). Autophagy and pancreatitis. American Journal of Physiology-Gastrointestinal and Liver Physiology, 303(9), G993–G1003. https://doi.org/10.1152/ajpgi.00122.2012
Ding, W. X., Ma, X., Kim, S., Wang, S., & Ni, H. M. (2024). Recent insights about autophagy in pancreatitis. eGastroenterology, 2(2), e100057. https://doi.org/10.1136/egastro-2023-100057
Ling, X., Zhang, Z., Lin, L., Guo, X., & Ding, Z. (2025). Dysfunction of autophagy in adipose tissue macrophages regulated via FoxO1 in obesity-related severe acute pancreatitis. International Journal of Molecular Sciences, 26(15), 7206. https://doi.org/10.3390/ijms26157206
Chen, H., Wang, Y., Zippi, M., Fiorino, S., & Hong, W. (2025). Oxidative stress, DAMPs, and immune cells in acute pancreatitis: Molecular mechanisms and therapeutic prospects. Frontiers in Immunology, 16, 1608618. https://doi.org/10.3389/fimmu.2025.1608618
Yang, S., Wang, X., Contino, G., Liesa, M., Sahin, E., Ying, H., Bause, A., Li, Y., Stommel, J. M., Dell’Antonio, G., Mautner, J., Tonon, G., Haigis, M., Shirihai, O. S., Doglioni, C., Bardeesy, N., & Kimmelman, A. C. (2011). Pancreatic cancers require autophagy for tumor growth. Genes & Development, 25(7), 717–729. https://doi.org/10.1101/gad.2016111
Perera, R. M., Stoykova, S., Nicolay, B. N., Ross, K. N., Fitamant, J., Boukhali, M., Lengrand, J., Deshpande, V., Selig, M. K., Ferrone, C. R., Settleman, J., Stephanopoulos, G., Dyson, N. J., Zoncu, R., Ramaswamy, S., Haas, W., & Bardeesy, N. (2015). Transcriptional control of autophagy-lysosome function drives pancreatic cancer metabolism. Nature, 524(7565), 361–365. https://doi.org/10.1038/nature14587
Yamamoto, K., Venida, A., Yano, J., Biancur, D. E., Kakiuchi, M., Gupta, S., Sohn, A. S. W., Mukhopadhyay, S., Lin, E. Y., Parker, S. J., Banh, R. S., Paulo, J. A., Wen, K. W., Debnath, J., Kim, G. E., Mancias, J. D., Fearon, D. T., Perera, R. M., & Kimmelman, A. C. (2020). Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I. Nature, 581(7806), 100–105. https://doi.org/10.1038/s41586-020-2229-5
Wolpin, B. M., Rizzato, C., Kraft, P., Kooperberg, C., Petersen, G. M., Wang, Z., Arslan, A. A., Beane-Freeman, L., Bracci, P. M., Buring, J., Canzian, F., Duell, E. J., Gallinger, S., Giles, G. G., Goodman, G. E., Goodman, P. J., Jacobs, E. J., Kamineni, A., Klein, A. P., . . . Amundadottir, L. T. (2014). Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. Nature Genetics, 46(9), 994–1000. https://doi.org/10.1038/ng.3052
Kocaturk, N. M., & Gozuacik, D. (2018). Crosstalk between mammalian autophagy and the ubiquitin-proteasome system. Frontiers in Cell and Developmental Biology, 6, 128. https://doi.org/10.3389/fcell.2018.00128
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Copyright (c) 2026 Jakub Motor, Michał Hajt, Dastin Misiaszek, Anna Wolszczak, Alicja Graczyk, Weronika Martynowska, Piotr Ciecierski, Natalia Grabowska, Zofia Parol

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