Department of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, Italy.
Biomedicine and Advanced Technologies Rieti Center, "Sabina Universitas", 02100 Rieti, Italy.
Cells. 2021 Sep 13;10(9):2408. doi: 10.3390/cells10092408.
ER lipid raft-associated protein 1 (ERLIN1) and 2 (ERLIN2) are 40 kDa transmembrane glycoproteins belonging to the family of prohibitins, containing a PHB domain. They are generally localized in the endoplasmic reticulum (ER), where ERLIN1 forms a heteroligomeric complex with its closely related ERLIN2. Well-defined functions of ERLINS are promotion of ER-associated protein degradation, mediation of inositol 1,4,5-trisphosphate (IP) receptors, processing and regulation of lipid metabolism. Until now, ERLINs have been exclusively considered protein markers of ER lipid raft-like microdomains. However, under pathophysiological conditions, they have been described within mitochondria-associated endoplasmic reticulum membranes (MAMs), tethering sites between ER and mitochondria, characterized by the presence of specialized raft-like subdomains enriched in cholesterol and gangliosides, which play a key role in the membrane scrambling and function. In this context, it is emerging that ER lipid raft-like microdomains proteins, i.e., ERLINs, may drive mitochondria-ER crosstalk under both physiological and pathological conditions by association with MAMs, regulating the two main processes underlined, survival and death. In this review, we describe the role of ERLINs in determining cell fate by controlling the "interchange" between apoptosis and autophagy pathways, considering that their alteration has a significant impact on the pathogenesis of several human diseases.
内质网脂质筏相关蛋白 1（ERLIN1）和 2（ERLIN2）是 40 kDa 的跨膜糖蛋白，属于抑素家族，含有 PHB 结构域。它们通常定位于内质网（ER）中，其中 ERLIN1 与其密切相关的 ERLIN2 形成异源寡聚复合物。ERLINs 的明确功能包括促进 ER 相关蛋白降解、介导肌醇 1,4,5-三磷酸（IP）受体、加工和调节脂质代谢。到目前为止，ERLINs 一直被认为是内质网脂质筏样微区的蛋白质标志物。然而，在病理生理条件下，它们已在与内质网和线粒体相连的内质网相关线粒体膜（MAMs）中被描述，其特征是存在富含胆固醇和神经节苷脂的特殊筏样亚区，在膜重排和功能中发挥关键作用。在这种情况下，新兴的观点认为，内质网脂质筏样微区蛋白，即 ERLINs，通过与 MAMs 结合，可能在生理和病理条件下驱动线粒体-内质网串扰，调节生存和死亡这两个主要过程。在这篇综述中，我们描述了 ERLINs 通过控制凋亡和自噬途径之间的“交换”来决定细胞命运的作用，考虑到它们的改变对几种人类疾病的发病机制有重大影响。
