Autophagy‐Dependent Ferroptosis as a Therapeutic Target in Cancer

Abstract

Ferroptosis is an iron-dependent form of cell death associated with the accumulation of labile iron and cytotoxic lipid peroxides. Increasing evidence reveals that ferroptosis is not a self-standing phenomenon and has close connections with other cellular events. Remarkably, recent insights show that ferroptosis is dependent on autophagy, which is a lysosomal degradation pathway responsible for the recycling of damaged cellular components under survival stress. Autophagy is capable of contributing to ferroptosis through degradation of the ferritin, an iron-storage protein, accompanied with the accumulation of iron levels and lipid ROS. The interplay between autophagy and ferroptosis also reveals emerging opportunities for novel tumor therapies, which has inspired the development of many treatment strategies capable of inducing ferroptosis in tumor cells via autophagic pathways based on molecular and nanoparticulate agents. In this review, we summarize the specific molecular and regulatory networks of autophagydependent ferroptosis and highlight their pathophysiological impact on various aspects of tumor cells. A perspective was also provided regarding the preliminary therapeutic exploitation of ferroptosis/autophagy crosstalk for tumor treatment.

Targeting ferroptosis in acute kidney injury

“…Disordered lysosomes recruit undigested substances, which ultimately contribute to lysosomal storage dysfunction. Recently, researchers have pointed out that lysosomes play a significant role in the formation of ferroptosis [ 74 – 76 ]. First, lysosomes are the major storage location for iron [ 77 ].…”

A Ferroptosis Molecular Subtype-Related Signature for Predicting Prognosis and Response to Chemotherapy in Patients with Chronic Lymphocytic Leukemia

“…In a previous report, ferroptosis was originally defined as a programmed cell death distinct from autophagy, apoptosis, and necrosis [ 7 ]. However, recent insights suggest that ferroptosis is not a self-standing phenomenon and has close connections with other cellular events [ 50 ]. For example, ferroptosis dependents on autophagy, especially selective types of autophagy, through direct or indirect regulation of iron accumulation or lipid peroxidation [ 50 , 51 ].…”

“…However, recent insights suggest that ferroptosis is not a self-standing phenomenon and has close connections with other cellular events [ 50 ]. For example, ferroptosis dependents on autophagy, especially selective types of autophagy, through direct or indirect regulation of iron accumulation or lipid peroxidation [ 50 , 51 ]. The top KEGG result is cytokine−cytokine receptor and the top 2 GSEA results are the hallmark gene sets of TNF α signaling via NF- κ B and inflammatory response.…”

Autophagy, Oxidative Stress and Cancer Development

“…Ferroptosis, an iron-related form of cell apoptosis, is defined as the accumulation of iron and cytotoxic lipid peroxides [ 155 ]. It was recently demonstrated that ferroptosis is related to autophagy through the degradation of ferritin, accompanied by an increment in intracellular iron and lipid ROS.…”

“…It was recently demonstrated that ferroptosis is related to autophagy through the degradation of ferritin, accompanied by an increment in intracellular iron and lipid ROS. The link between autophagy and ferroptosis may give rise to future anticarcinogenic treatment options [ 155 ]; however, more research is warranted to further elucidate this issue.…”