Autophagy and Its Role in Animal Diseases

Yıl 2023, , 28 - 36, 31.03.2023

Sinem İnal , Yonca Betil Kabak

https://doi.org/10.35229/jaes.1210073

Öz

Autophagy is a term of Greek origin and means self (auto) eating (phagy). It can be defined as the cell confining its cytoplasmic content or intracellular pathogens with a membrane. This membrane merges with the lysosome in mammalian cells to form the phagolysosome structure. In the early 1960s, yeasts were used to investigate autophagy mechanisms and identify related genes. The autophagic activity was observed in yeasts incubated under different conditions. Autophagy occurs in the normal physiological process of the cell; thus, cytoplasmic products, especially old cellular organelles, are eliminated. The final products formed after fragmentation are offered for the use of the cell again. This way, it works as a recycling mechanism that supports the cell's energy balance. Disruption in the autophagy mechanism causes many problems, such as infection, cancer and neurodegenerative diseases. The relationship between autophagy and human diseases has been well documented. However, in addition to experimental studies, investigating the role of autophagy in animal diseases is essential in veterinary medicine. It is aimed to review the literature data on autophagy and current reports on the role of autophagy in essential animal diseases.

Anahtar Kelimeler

autophagy, phagolysosome, yeast

Otofaji ve Hayvan Hastalıklarında Rolü

Öz

Otofaji, Yunanca kökenli bir terim olup kelime anlamı olarak kendi kendini (auto) yeme (phagy) anlamına gelmektedir. Hücrenin kendi sitoplazmik içeriğinin veya hücre içi patojenlerin bir zarla sınırlaması şeklinde tanımlanabilir. Bu zar yapısı memeli hücrelerinde lizozomla birleşerek fagolizozom yapısını oluşturmaktadır. 1960’lı yılların başında otofaji mekanizmalarının daha iyi anlaşılması ve ilgili genlerin belirlenebilmesi için mayalardan yararlanılmıştır. Mayalar farklı şartlarda inkube edildiğinde otofajik aktivite gözlenmiştir. Otofaji hücrenin normal fizyolojik süreci içinde bulunmakta ve bu işlem sayesinde eski hücresel organeller başta olmak üzere sitoplazmik ürünler parçalanmaktadır. Parçalanma sonrası meydana gelen son ürünler yeniden hücrenin kullanımına sunulmaktadır. Böylelikle hücrenin enerji dengesine katkı sağlayan bir geri dönüşüm mekanizması olarak çalışmaktadır. Otofaji mekanizmalarında meydana gelecek sorunlar enfeksiyon, kanser ve nörodejeneratif hastalıklar gibi birçok problemin görülmesine neden olmaktadır. Otofaji ve insan hastalıkları arasındaki ilişki yoğun olarak çalışılmıştır. Ancak deneysel çalışmaların yanı sıra hayvan hastalıklarında da otofajinin rolünün araştırılması veterinerlik alanında önemlidir. Bu derlemenin amacı, otofaji hakkındaki literatür verisinin taranması, önemli hayvan hastalıklarında otofajinin rolüyle ilgili güncel bilgilerin derlenmesidir.

Anahtar Kelimeler

Fagolizozom, maya, otofaji, autophagy, phagolysosome

Kaynakça

• Anding, A.L. & Baehrecke, E.H. (2015). Autophagy in cell life and cell death. Current Topics in Developmental Biology, 114, 67-91.
• Arslan, D.Ö., Korkmaz, G. & Gözüaçık, D. (2011). Otofaji: Bir Hücresel Stres Yanıtı ve Ölüm Mekanizması. Acıbadem Üniversitesi Sağlık Bilimleri Dergisi, 2(4), 184-194.
• Ávila-Pérez, G., Diaz-Beneitez, E., Cubas-Gaona, L.L., Nieves-Molina, G., Rodríguez, J.R., Rodriguez, J.F. & Rodriguez, D. (2019). Activation of the autophagy pathway by Torovirus infection is irrelevant for virus replication. Plos One, 14(7), 1- 28.
• Baba, M., Osumi, M. & Ohsumi, Y. (1995). Anaysis of the membrane structures involved in autophagy in yeast by freeze-replica method. Cell Structure and Function, 20(6), 465-471.
• Baba, M., Takeshige, K., Baba, N., & Ohsumi, Y. (1994). Ultrastructural analysis of the autophagic process in yeast: detection of autophagosomes and their characterization. Journal of Cell Biology, 124(6), 903-913.
• Braunbeck, T. & Storch, V. (1992). Senescence of hepatocytes isolated from rainbow trout (Oncorhynchus mykiss) in primary culture. Protoplasma, 170(3), 138-159.
• Chang, Y.Y. & Neufeld, T.P. (2009). An Atg1/Atg13 complex with multiple roles in TOR-mediated autophagy regulation. Molecular Biology of the Cell, 20(7), 2004-2014.
• Cheng, C.Y., Tseng, H.H., Chiu, H.C., Chang, C.D., Nielsen, B.L. & Liu, H.J. (2019). Bovine ephemeral fever virus triggers autophagy enhancing virus replication via upregulation of the Src/JNK/AP1 and PI3K/Akt/NF-κB pathways and suppression of the PI3K/Akt/mTOR pathway. Veterinary Research, 50(1), 1-15.
• Delpeut, S., Rudd, P.A., Labonté, P. & Von Messling, V. (2012). Membrane fusion-mediated autophagy induction enhances morbillivirus cell-to-cell spread. Journal of Virology, 86(16), 8527-8535.
• Dong, X. & Levine, B. (2013). Autophagy and viruses: adversaries or allies? Journal of Innate Immunity, 5(5), 480-493.
• Ferreira, J.V., Fôfo, H., Bejarano, E., Bento, C.F., Ramalho, J.S., Girão, H. & Pereira, P. (2013). STUB1/CHIP is required for HIF1A degradation by chaperone-mediated autophagy. Autophagy, 9(9), 1349-1366.
• Glick, D., Barth, S. & Macleod, K.F. (2010). Autophagy: cellular and molecular mechanisms. Journal of Pahology, 221(1), 3-12.
• Gou, H., Zhao, M., Fan, S., Yuan, J., Liao, J., He, W., Xu, H. & Chen, J. (2017). Autophagy induces apoptosis and death of T lymphocytes in the spleen of pigs infected with CSFV. Scientific Reports, 7(1), 1-11.
• Green, D.R. & Levine, B. (2014). To be or not to be? How selective autophagy and cell death govern cell fate. Cell, 157(1), 65-75.
• Guo, M., Wu, F., Zhang, Z., Hao, G., Li, R., Li, N., Shang, Y., Wei, L. & Chai, T. (2017). Characterization of rabbit nucleotide-binding oligomerization domain 1 (NOD1) and the role of NOD1 signaling pathway during bacterial infection. Frontiers in Immunology, 8, 1-15.
• He, C. & Klionsky, D.J. (2009). Regulation mechanisms and signaling pathways of autophagy. Annual Review of Genetics, 43(1), 67-93.
• Heitman, J., Movva, N.R. & Hall, M.N. (1991). Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science, 253(5022), 905-909.
• Hoet, A. & Horzinek, M. (2008). Torovirus. Encyclopedia of Virology, 151-157p, Elsevier.
• Hosokawa, N., Hara, T., Kaizuka, T., Kishi, C., Takamura, A., Miura, Y., Iemura, S.I., Natsume, T., Takehana, K. & Yamada, N. (2009). Nutrient-dependent mTORC1 association with the ULK1–Atg13–FIP200 complex required for autophagy. Molecular Biology of the Cell, 20(7), 1981-1991.
• Hou, L., Wei, L., Zhu, S., Wang, J., Quan, R., Li, Z. & Liu, J. (2017). Avian metapneumovirus subgroup C induces autophagy through the ATF6 UPR pathway. Autophagy, 13(10), 1709-1721.
• Izmirli, M., Ecevit, H. & Göğebakan, B. (2014). Yaşamak için Otofaji. Arşiv Kaynak Tarama Dergisi, 23(3), 411-419.
• Jung, C.H., Jun, C.B., Ro, S.-H., Kim, Y.M., Otto, N.M., Cao, J., Kundu, M. & Kim, D.-H. (2009). ULKAtg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Molecular Biology of the Cell, 20(7), 1992-2003.
• Jung, C.H., Ro, S.H., Cao, J., Otto, N.M. & Kim, D.H. (2010). mTOR regulation of autophagy. FEBS Letters, 584(7), 1287-1295.
• Kabak, Y., Sozmen, M., Yarim, M., Guvenc, T., Karayigit, M. & Gulbahar, M. (2015). Immunohistochemical detection of autophagyrelated microtubule-associated protein 1 light chain 3 (LC3) in the cerebellums of dogs naturally infected with canine distemper virus. Biotechnic & Histochemistry, 90(8), 601-607.
• Kang, R., Zeh, H., Lotze, M. & Tang, D. (2011). The Beclin 1 network regulates autophagy and apoptosis. Cell Death and Differentiation, 18(4), 571-580.
• Kang, Y., Yuan, R., Xiang, B., Zhao, X., Gao, P., Dai, X., Liao, M. & Ren, T. (2017). Newcastle disease virus-induced autophagy mediates antiapoptotic signaling responses in vitro and in vivo. Oncotarget, 8(43), 73981-73993.
• Karadağ, A. (2016). Otofaji: Programlı Hücre Ölümü. Ankara Sağlık Hizmetleri Dergisi, 15(2), 19-26.
• Khaminets, A., Behl, C. & Dikic, I. (2016). Ubiquitindependent and independent signals in selective autophagy. Trends in Cell Biology, 26(1), 6-16.
• Kirisako, T., Ichimura, Y., Okada, H., Kabeya, Y., Mizushima, N., Yoshimori, T., Ohsumi, M., Takao, T., Noda, T. & Ohsumi, Y. (2000). The reversible modification regulates the membranebinding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway. Journal of Cell Biology, 151(2), 263- 276.
• Klionsky, D.J. (2005). The molecular machinery of autophagy: unanswered questions. Journal of Cell Science, 118(1), 7-18.
• Klionsky, D.J., Cregg, J.M., Dunn, W.A., Emr, S.D., Sakai, Y., Sandoval, I.V., Sibirny, A., Subramani, S., Thumm, M. & Veenhuis, M. (2003). A unified nomenclature for yeast autophagy-related genes. Developmental Cell, 5(4), 539-545.
• Kocatürk, N.M. & Gözüaçık, D. (2017). Otofaji ve Nörodejeneratif Hastalıklar. Turkiye Klinikleri Journal of Pharmacology-Special Topics, 5(1), 11-20.
• Kornicka, K., Al Naem, M., Röcken, M., Zmiertka, M. & Marycz, K. (2019). Osteochondritis dissecans (OCD)-derived chondrocytes display increased senescence, oxidative stress, chaperone-mediated autophagy and, in co-culture with adipose-derived stem cells (ASCs), enhanced expression of MMP13. Journal of Clinical Medicine, 8(3), 1-22.
• Levine, B. & Yuan, J. (2005). Autophagy in cell death: an innocent convict? The Journal of Clinical Investigation, 115(10), 2679-2688.