Ferroptosis: A Double-Edged Sword in Gastrointestinal Disease.

Chengfei Xu,Ziling Liu,Jiangwei Xiao

doi:10.3390/ijms222212403

Chengfei Xu, Ziling Liu + Show 1 more

Open Access

https://doi.org/10.3390/ijms222212403

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Abstract

Ferroptosis is a novel form of regulated cell death (RCD) that is typically accompanied by iron accumulation and lipid peroxidation. In contrast to apoptosis, autophagy, and necroptosis, ferroptosis has unique biological processes and pathophysiological characteristics. Since it was first proposed in 2012, ferroptosis has attracted attention worldwide. Ferroptosis is involved in the progression of multiple diseases and could be a novel therapeutic target in the future. Recently, tremendous progress has been made regarding ferroptosis and gastrointestinal diseases, including intestinal ischemia/reperfusion (I/R) injury, inflammatory bowel disease (IBD), gastric cancer (GC), and colorectal cancer (CRC). In this review, we summarize the recent progress on ferroptosis and its interaction with gastrointestinal diseases. Understanding the role of ferroptosis in gastrointestinal disease pathogenesis could provide novel therapeutic targets for clinical treatment.

Highlights

Since 2012, ferroptosis has been identified as a novel form of regulated cell death (RCD) that differs from necroptosis, apoptosis, and autophagy [1]
As a novel type of regulated cell death, ferroptosis is characterized by the accumulation of cellular iron and toxic phospholipids
The induction of ferroptosis using pharmacological agonists or bioactive compounds inhibits the proliferation of gastric cancer (GC) and colorectal cancer (CRC)

Summary

Introduction

Since 2012, ferroptosis has been identified as a novel form of regulated cell death (RCD) that differs from necroptosis, apoptosis, and autophagy [1]. (1) The canonical pathway to regulate ferroptosis is the xc – –glutathione (GSH)-dependent pathway, which was first proposed in 2014 (pathway 1 in Figure 1) [5,6]. FSP1 is the predominant ferroptosis resistance factor in this pathway, which catalyzes the conversion of ubiquinone to ubiquinol and prevents lipid peroxidation in the cellular membrane. DHODH mediates ferroptosis by reducing ubiquinone to ubiquinol, which occurs in the mitochondria. Ferroptosis is triggered byaccumulation the accumulation of oxidized and phostoxic pholipids. We present the three potential regulatory pathways of ferroptosis.

Crucial Modulators of Ferroptosis

Polyunsaturated Fatty Acids

Cellular Iron Pool

The Role of Ferroptosis in IBD

Findings

Conclusions and Perspectives