Baig Saad Ilyas, Naseer Maria, Munir Abdur-Rehman, Ali Yasir, Razzaq Muhammad Asif
Department of Biotechnology, University of Central Punjab, Lahore, Pakistan.
Biogerontology. 2024 Nov;25(6):1189-1213. doi: 10.1007/s10522-024-10130-w. Epub 2024 Aug 28.
The CISD protein family, consisting of CISD1, CISD2, and CISD3, encodes proteins that feature CDGSH iron-sulfur domains crucial for cellular functions and share a common 2Fe-2S domain. CISD2, which is pivotal in cells, regulates intracellular calcium levels, maintains the endoplasmic reticulum and mitochondrial function, and is associated with longevity and overall health, with exercise stimulating CISD2 production. However, CISD2 expression decreases with age, impacting age-related processes. According to in silico docking, HST is a CISD2 activator that affects metabolic dysfunction and age-related illnesses by affecting metabolic pathways. This study investigated the ability of CISD2 and HST to reduce age-related ailments, with a particular emphasis on liver aging. CISD2 deficiency has a major effect on the function of cells, as it undermines the integrity of the ER, mitochondria, and calcium homeostasis. It also increases susceptibility to oxidative stress and metabolic dysregulation, which is linked to Wolfram syndrome and exacerbates age-related illnesses and metabolic disorders. By shielding cells from stress, CISD2 extends the life of cells and maintains liver health as people age. Its protective effecfts on the liver during aging are further enhanced by its control of translation factors such as Nrf2 and IL-6. This work paves the way for future investigations and clinical applications by examining the structural and functional properties of CISD2 and the interaction between CISD2 and HST. This highlights the therapeutic potential of these findings in promoting healthy livers in humans and battling age-related illnesses.
CISD蛋白家族由CISD1、CISD2和CISD3组成，其编码的蛋白质具有对细胞功能至关重要的CDGSH铁硫结构域，并共享一个共同的2Fe-2S结构域。CISD2在细胞中起关键作用，调节细胞内钙水平，维持内质网和线粒体功能，并与长寿和整体健康相关，运动可刺激CISD2的产生。然而，CISD2的表达会随着年龄增长而下降，影响与年龄相关的过程。根据计算机对接分析，HST是一种CISD2激活剂，通过影响代谢途径来影响代谢功能障碍和与年龄相关的疾病。本研究调查了CISD2和HST减轻与年龄相关疾病的能力，特别关注肝脏衰老。CISD2缺乏对细胞功能有重大影响，因为它破坏了内质网、线粒体的完整性以及钙稳态。它还增加了对氧化应激和代谢失调的易感性，这与沃夫勒姆综合征有关，并加剧了与年龄相关的疾病和代谢紊乱。通过保护细胞免受应激，CISD2可延长细胞寿命，并随着人们年龄的增长维持肝脏健康。在衰老过程中，它对肝脏的保护作用通过对Nrf2和IL-6等翻译因子的控制而进一步增强。这项工作通过研究CISD2的结构和功能特性以及CISD2与HST之间的相互作用，为未来的研究和临床应用铺平了道路。这突出了这些发现在促进人类肝脏健康和对抗与年龄相关疾病方面的治疗潜力。
