HÜCRE KORUYUCU BİR MEKANİZMA: OTOFAJİ

Year 2017, Volume: 26 Issue: 3, 275 - 281, 01.12.2017

Narin Liman Duygu Cemre Suna

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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