The Role of CISD2 in Autophagy of Endoplasmic Reticulum

Date

2024

Journal Title

Journal ISSN

Volume Title

Publisher

Tartu Ülikool

Abstract

Wolfram syndrome (WS) is an uncommon neurological condition distinguished by the presence of diabetes insipidus, diabetes mellitus, optic atrophy, and hearing loss. The condition is attributed to genetic alterations in either the WFS1 gene (WS1) or the CISD2 gene (WS2). CISD2 genes for a 15-kDa transmembrane protein that is found in the endoplasmic reticulum (ER). It is involved in several cellular functions such as maintaining calcium and iron levels, as well as regulating autophagy. This work examines the function of CISD2 in autophagy, specifically focusing on ER-phagy, which is a type of selective autophagy that targets the endoplasmic reticulum. We utilized HeLa cell models with CISD2 deletion (CISD2-KO) and wild-type (CISD2-WT) conditions to evaluate the levels of ER-phagy using confocal microscopy and Western blot analysis. The findings suggest that the lack of CISD2 results in heightened ER-phagy, whereas its presence or excessive expression diminishes ER-phagy, hence illustrating the protective function of CISD2. Furthermore, it was demonstrated that interaction partners such as CISD1 and Bcl-2 had an impact on ER-phagy in cells lacking CISD2, indicating prospective targets for therapeutic intervention in disorders related to CISD2 deficiency. This study offers valuable information about the functional role of CISD2 in ER-phagy and its possible implications in WS2 and other related diseases.

Description

Keywords

Wolfram syndrome, CISD2, Autophagy, ER-phagy, HeLa cells, CISD1, bcl-2, CISD2 overexpression

Citation