Memeli hücrelerinde otofajinin moleküler mekanizması

Year 2017, Volume: 5 Issue: 2, 205 - 218, 25.12.2017

Yasemin Sahın Dilara Akcora Yıldız

https://doi.org/10.24998/maeusabed.355164

Abstract

Mayadan insana kadar
evrimsel olarak korunmuş bir mekanizma olan makrootofaji (bundan sonra otofaji),
hücreleri açlıktan ve buna bağlı streslerden korumakta ve makromolekülleri
enerji sağlamak için kullanılabilecek olan yapı taşlarına indirgemektedir.
Otofaji, bir parça sitoplazma yığınını, organelleri (örneğin mitokondri ve
peroksizomlar), agregat oluşturmaya eğilim gösteren proteinleri ve enfeksiyöz
ajanları otofagozomlar olarak adlandırılan çift-membranlı veziküllerle
lizozomlara taşıyan hücre içi degredasyon yoludur. Memeli sistemi üzerine
yapılan çalışmalar, sağlık ve hastalıkta otofajinin diğer önemli rollerini
göstermiştir. Klinik öncesi hem
nörodejeneratif hem de enfeksiyöz hastalıklarla ilgili hayvan modellerinde
yapılan araştırmalar, otofaji upregülasyonunun, demans formları (tau'nun neden
olduğu), Parkinson hastalığı (α-sinüklein) ve Huntington hastalığı (mutant
huntingtin) gibi çeşitli nörodejeneratif hastalıklara neden olan agregata
eğilimli intrasitoplazmik proteinlerin degradasyonunda; Salmonella typhi ve Mycobacterium
tuberculosis gibi patojenik ajanlardan kaynaklanan belli bulaşıcı hastalıklara
karşı korunmada önemli bir rol oynadığını göstermiştir. Fare hematopoietik kök
hücrelerin (HSCs) devamlılığının sürdürülmesinde gerekliliği vurgulanan
otofaji, fonksiyonelliği bozulduğunda HSC'leri normalden pre-lökemik bir duruma
geçirmektedir. Mutasyonlar veya önemli otofaji regülatörlerinin ifadelerinin
azalması nedeniyle otofajik aktivitede gerçekleşen düşüş, pre-lösemi gelişimini
desteklerken, bu mekanizmanın tedavide kullanılan ajanlarla yeniden
etkinleştirilmesi hastalığın nüksetmesine yol açmaktadır. Otofaji aktivasyon
düzeyi, kanser progresyonu ile anabolik ve katabolik işlemlerde üstlendiği
rollerden dolayı obezite ve metabolik hastalıklarda önemli rol oynamaktadır.
Otofajinin sağlıkta ve çeşitli hastalıkların patogenezindeki moleküler
mekanizmalarına ilişkin çalışmaların sayısı gün geçtikçe artmaktadır. Bu
derlemede, memeli hücrelerinde gerçekleşen otofaji ve moleküler mekanizması
hakkında genel bir bakış sunulması ve bilgi verilmesi amaçlanmıştır.

Keywords

otofaji, memeli hücresi, moleküler mekanizma

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