Emerging Roles of Energy Metabolism in Ferroptosis Regulation of Tumor Cells

Abstract

Ferroptosis is a new form of regulated cell death, which is characterized by the iron-dependent accumulation of lethal lipid peroxides and involved in many critical diseases. Recent reports revealed that cellular energy metabolism activities such as glycolysis, pentose phosphate pathway (PPP), and tricarboxylic acid cycle are involved in the regulation of key ferroptosis markers such as reduced nicotinamide adenine dinucleotide phosphate (NADPH), glutathione (GSH), and reactive oxygen species (ROS), therefore imposing potential regulatory roles in ferroptosis. Remarkably, tumor cells can activate adaptive metabolic responses to inhibit ferroptosis for self-preservation such as the upregulation of glycolysis and PPP. Due to the rapid proliferation of tumor cells and the intensified metabolic rate, tumor energy metabolism has become a target for disrupting the redox homeostasis and induce ferroptosis. Based on these emerging insights, regulatory impact of those-tumor specific metabolic aberrations is systematically characterized, such as rewired glucose metabolism and metabolic compensation through glutamine utilization on ferroptosis and analyzed the underlying molecular mechanisms. Additionally, those ferroptosis-based therapeutic strategies are also discussed by exploiting those metabolic vulnerabilities, which may open up new avenues for tumor treatment in a clinical context.

Exploring the Association between Glutathione Metabolism and Ferroptosis in Osteoblasts with Disuse Osteoporosis and the Key Genes Connecting them

“…Cell death is caused by a variety of mechanisms. Cell death modes include autophagy, pyroptosis, Wallerian degeneration, excitotoxicity, and ferroptosis [ 6 – 8 ]. Ferroptosis is a nonapoptotic cell death mode, which is significantly different from other programmed cell death [ 9 ].…”

The lncRNA BDNF-AS/WDR5/FBXW7 axis mediates ferroptosis in gastric cancer peritoneal metastasis by regulating VDAC3 ubiquitination

“…Previous studies indicated that VDAC3 could affect cell ferroptosis by regulating the mitochondrial entry and exit of iron ions 19 , 20 , 45 . Excessive iron accumulation could result in ROS production through the Fenton reaction and then cause ferroptosis 46 , 47 . Our results showed that when BDNF-AS was overexpressed, the VDAC3 protein expression level increased.…”

Single-Cell RNA-Seq Reveals the Promoting Role of Ferroptosis Tendency During Lung Adenocarcinoma EMT Progression

“…As the site for intracellular oxidative respiration, mitochondrion is a major source of ROS. By promoting mitochondrial respiration, the ferroptosis promoter erastin can increase the production of ROS and thus promote ferroptosis by enhancing mitochondrial respiration ( Yao et al, 2021b ). Combined with the results of the above causal inference, we believe that ferroptosis leads to the low expression of GPX4, which promotes the accumulation of ROS and reduces the inhibition of CDH2 expression, thereby promoting the occurrence of EMT.…”