Research progress on the mechanism of activating transcription factor 5 in regulating cellular inflammatory stress response.
10.3760/cma.j.cn121430-20240729-00637
- Author:
Haiyun LEI
1
,
2
;
Bao FU
;
Xiaoyun FU
Author Information
1. Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, China. Corresponding author: Fu Xiaoyun, Email: fxycloudy@
2. com.
- Publication Type:English Abstract
- MeSH:
Humans;
Endoplasmic Reticulum Stress;
Inflammation/metabolism*;
Activating Transcription Factors/metabolism*;
Unfolded Protein Response;
Mitochondria/metabolism*;
Apoptosis;
Animals
- From:
Chinese Critical Care Medicine
2025;37(5):499-504
- CountryChina
- Language:Chinese
-
Abstract:
Activating transcription factor 5 (ATF5) is a member of the activating transcription factor/cyclic adenosine monophosphate response element binding protein (ATF/CREB) family. As a stress-induced transcription factor, ATF5 plays a crucial role in cellular inflammatory stress responses. Under cellular inflammatory stress conditions, ATF5 maintains cell homeostasis and survival by regulating key genes in the mitochondrial unfolded protein response (UPRmt) and endoplasmic reticulum stress (ERS). As a key regulator in UPRmt, ATF5 senses mitochondrial stress and translocate to the nucleus to activate the transcription of UPRmt-related genes, thereby promoting mitochondrial function recovery. Meanwhile, in ERS, ATF5 maintains endoplasmic reticulum homeostasis by regulating the expression of genes related to protein folding, degradation, and apoptosis, determining cell survival or death. ATF5 plays a vital role in various cellular inflammatory stress responses. In infectious inflammation, ATF5 plays an important role in alleviating neuroinflammation and maintaining intestinal barrier function by regulating UPRmt. In inflammation related to degenerative diseases, ATF5 improves intervertebral disc degeneration and delays the progression of osteoarthritis by regulating UPRmt. In metabolic inflammation such as diabetes and obesity, ATF5 regulates UPRmt and ERS to maintain the function of pancreatic β-cells, controlling their survival or inducing apoptosis, thus influencing the progression of diabetes. ATF5 protects mitochondria in the kidneys, adipose tissue, and pancreas, slows the progression of diabetic nephropathy, and improves insulin sensitivity. Furthermore, in immune-related inflammation, ATF5 alleviates glomerulonephritis and promotes tissue repair by enhancing immune tolerance in dendritic cells. In summary, ATF5, as a key regulator in cellular inflammatory stress responses, maintains cell homeostasis through regulating UPRmt and ERS and determines cell fate. Its critical regulatory role in cellular inflammatory stress responses makes ATF5 a potential clinical therapeutic target. This article summarizes the structural features and translational regulatory mechanisms of ATF5, focusing on its role in cellular inflammatory stress responses, particularly its regulatory mechanisms in UPRmt and ERS, aiming to provide a theoretical basis for understanding ATF5's role in cell and organ protection and to offer new insights into the treatment of related inflammatory diseases.
