Characteristics and Biomarkers of Ferroptosis

Abstract

The induction and consequences of regulated cell death (RCD) are accompanied by changes in gene and protein expression, biochemical pathways, as well as cell morphology and size. Such RCDs have a significant impact on development, tissue homeostasis, and the occurrence and progression of disease. Among different forms of RCD, ferroptosis appears to be the main cause of tissue damage driven by iron overload and lipid peroxidation. In fact, the dysfunctional ferroptotic response is implicated in a variety of pathological conditions and diseases, such as neurodegenerative diseases, tissue ischemia-reperfusion injury, tumorigenesis, infections, and immune diseases. Ferroptotic response can be fine-tuned through various oxidative stress and antioxidant defense pathways, coupling with metabolism, gene transcription, and protein degradation machinery. Accordingly, a series of ferroptosis inducers or inhibitors targeting redox- or iron metabolism-related proteins or signal transduction have been developed. Although this kind of RCD has recently attracted great interest in basic and clinical research, detecting and monitoring a ferroptotic response still faces challenges. In this mini-review, we not only summarize the latest knowledge about the characteristics of ferroptosis in vitro and in vivo, but also discuss the specificity and limitations of current biomarkers of ferroptosis.

The Activation of Endothelial Cells Relies on a Ferroptosis-Like Mechanism: Novel Perspectives in Management of Angiogenesis and Cancer Therapy

“…So far, there are no specific markers of ferroptosis as a cell death mechanism and because we were exploring the non-lethal effect of ferroptosis, in this work we evaluated the levels of ROS-induced lipids peroxides underlying ferroptosis and GSH dynamics (67). The expression of genes pointed as being decreased upon ferroptosis activation, PTGS2, GPX4 and GSS was also assessed (10,(68)(69)(70). In our experimental conditions, we observed that Erastin significantly decreases cyst(e)ine uptake (Figure 1E) and promotes the increase of intracellular ROS (Figure 1A) and lipid peroxide levels (Figure 1C), without affecting the mitochondrial ROS content (Figure 1B).…”

Knowledge Domain and Emerging Trends in Ferroptosis Research: A Bibliometric and Knowledge-Map Analysis

“…In the rapid development stage (2018-now), emerging topics, such as breast cancer, iron metabolism, degradation, nanoparticle, biology, did not only continue the characteristics of the stable-growth stage but also used more technology, such as the emerging application of nanoparticles in cancer treatment (61)(62)(63)(64)(65)(66)(67). Unfortunately, although many essential regulatory molecules were demonstrated and transferrin receptor 1 protein (TfR1) was considered as a specific marker of ferroptosis by some scholars (68), there are still no acknowledged specific biomarkers of ferroptosis, such as caspase activation for apoptosis or autophagy lysosome formation for autophagy (9,69).…”

Targeting GRK5 for Treating Chronic Degenerative Diseases

“…Indeed, p53 is involved in several biological and pathological processes and recently, it has been associated with the regulation of ferroptosis [130]. This iron-dependent new form of programmed cell death is driven by lipid peroxidation and is involved in cancer, tissue ischemia/reperfusion injury, and neurodegeneration [130,131]. Whether and how GRK5 via p53 regulates ferroptosis is an urgent question that deserves an immediate response.…”