HÜCRE KORUYUCU BİR MEKANİZMA: OTOFAJİ

Abstract

Otofaji (kendini yeme) hasarlı hücresel proteinleri ve organelleri ortadan kaldıran evrimsel bir süreçtir. Otofaji uyarılınca bozunuma uğrayan sitoplazma ve organeller veziküller içine alınır. Şekillenen veziküller mayalarda vakuole, memeli hücrelerinde lizozoma gönderilir. Açlık veya oksidatif stres gibi durumlarda ya da normal koşullar altında makromoleküllerin bozunumu ve besin dengesinin sağlanması otofaji aracılığıyla düzenlenir. Ökaryotik hücrelerde otofaji, oluşma şekline göre makro-otofaji, mikro-otofaji ve şaperon aracılı otofaji olarak sınıflandırılır. Bunların hepsi lizozomda sitosolik bileşenlerin proteolitik bozunmasını teşvik eder ve otofajiye bağlı genler ve bunlarla ilişkili enzimler aracılığıyla düzenlenirler. Makro-otofaji ve mikrootofaji bağımlı lizozomal/vakuoler yıkım süreci ya seçici olmaz (non-selektif) ya da seçicidir (selektif). Şaperon aracılı otofaji yanlış katlanmış veya yanlışlıkla oluşturulmuş sitosolik proteinleri indirgemek için kullanılan bir seçici otofajidir. Seçici olmayan makrootofajide sitoplazma otofagozom oluşumuyla, mikrootofajide ise çözünebilir intrasellüler substratlar boru biçimindeki invaginasyonlarla lizozom/vakuol içine alınır. Seçici makro- ya da mikro-otofaji sayısı artan ya da hasar görmüş olan çeşitli organeller ile invaziv mikropları hedef alır. Bu durumda otofaji kargo içeriğine göre retikulofaji veya ERfaji, pekzofaji, mitofaji, lipofaji, zimofaji, nükleofaji, ribofaji, agrefaji ve ksenofaji gibi özel isimlerle tanımlanır. Bu derlemede doğru hücresel fonksiyonları korumak için hasarlı organelleri, protein yığınlarını ve hücre içi patojenleri yok eden bir sitoprotektif program olarak işlev gören otofaji ele alınmıştır.

Keywords

• Otofaji, lizozom, vakuol, ULK1, TOR

A Cytoprotective Mechanism: Autophagy

Abstract

Autophagy (self-eating) is an evolutionary process that removes damaged cellular proteins and organelles. When autophagy is induced, degrading cytoplasm and organelles are taken up into vesicles. . These vesicles are sent to the vacuolated or lysosomes in the yeast and mammalian cells, respectively. Provision of degradation of macromolecules and nutrient balance under stress conditions, such as starvation or oxidative stress or under normal conditions, is regulated by autophagy. In eukaryotic cells, autophagy is classified as macroautophagy, micro-autophagy and chaperone-mediated autophagy according to the formation pattern. All of these promote the proteolytic degradation of cytosolic components in the lysosome and are regulated by autophage-linked genes and their associated enzymes. Macro-autophagy and micro-autophagy dependent lysosomal/vacuolar degradation processes are either non-selective or selective (selective). Chaperonemediated autophagy is a selective autophagy used to reduce unfolded or misfolded cytosolic proteins. In the non-selective macro-autophagy, the cytoplasm is incorporated into the lysosome/vacuole by autophagosome, while in the micro-autophagy the soluble intracellular substrates are introduced into the lysosome/vacuole via tubular invaginations. The selective macro- or micro-autophagy target invasive microorganisms with various organelles that are either increased in number or damaged. In this case, autophagy is defined by special names such as reticulophagy or ERphagy, pexophagy, mitophagy, lipophagy, zimophagy, nucleophagy, ribophagy, aggrephagy and ksenophagy, according to the contents of the cargo. This review focuses on autophagy that functions as a cytoprotective program that destroys damaged organelles, protein deposits and intracellular pathogens in order to preserve the correct cellular functions.

Keywords

• Autophagy, lysosome, vacuole, ULK1, TOR

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