Endoplazmik Retikulumda Katlanmamış Protein Cevabı ile İlişkili Hastalıklar

Endoplazmik retikulum (ER), sekretuar yolağın ilk kompartımanı olup eritrosit ve sperm hücreleri gibi oldukça özelleşmiş ökaryotik hücreler hariç büyük ölçüde tüm hücrelerde bulunan, çift katmanlı membranöz intraselüler bir organeldir. ER birçok hücresel fonksiyona dahil olmaktadır. Hücresel proteinlerin yaklaşık 1/3’ünün üretiminde ve katlanmasında görev alıp hücresel homeostazın devamlılığını sürdürmekle görevlidir. Protein üretim fabrikası gibi çalışması yanında, Ca+2 depolama ve düzenleme, lipit üretme ve depolama ve glikoz metabolizması işlemlerine de dahil olmaktadır. Bu görevlerin yanında ER homeostazını sürdürebilmek için, ER stres sinyal yolakları olan “Katlanmamış Protein Cevabı” ile hücre homeostazı sağlanmaya çalışılır. ER homeostazı, hatalı ya da katlanmamış protein katlanması ve mutant protein birikmesinin dahil olduğu birçok patolojik olayla ilişkili olarak ER stresine sebebiyet verebilmektedir. Bu derlemede endoplazmik retikulumun katlanmamış protein cevabı ve katlanmamış protein cevabı ile ilişkili hastalıklar tartışılmıştır.

Unfolded Protein Response Related Diseases in Endoplasmic Reticulum

The endoplasmic reticulum (ER) is the first compartment of the secretory pathway and is a bilayer membranous intracellular organelle found in almost all cells except highly specialized eukaryotic cells such as erythrocytes and sperm cells. The ER is involved in many different cellular functions. ER contributes to the production and folding of approximately one-third of cellular proteins, and plays an important role for the maintenance of cellular homeostasis. In addition to, it acts as a protein synthesis factory, contributes to the storage and regulation of calcium, to the synthesis and storage of lipids, and glucose metabolism. Besides these features, specific ER stress signaling pathways, known as the ‘unfolded protein response’, are required for maintaining ER homeostasis. ER homeostasis can be given cause for many pathological events, including protein misfolding or accumulation of mutant protein, which can lead to ER stress. In this review, unfolded protein response of the endoplasmic reticulum and diseases associated with unfolded protein response are discussed.

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