Role of mitochondria in the regulation of ferroptosis and disease

Abstract

Ferroptosis is a distinctive form of iron-dependent cell death characterized by significant ultrastructural changes in mitochondria. Given the crucial involvement of mitochondria in various cellular processes such as reactive oxygen species production, energy metabolism, redox status, and iron metabolism, mounting evidence suggests a vital role of mitochondria in the regulation and execution of ferroptosis. Furthermore, there exists a strong correlation between ferroptosis and various diseases. In this review, we aim to summarize the mechanisms underlying the induction and defense of ferroptosis, emphasizing the influence of mitochondria on this intricate process. Additionally, we provide an overview of the role of ferroptosis in disease, particularly cancer, and elucidate the mechanisms by which drugs targeting mitochondria impact ferroptosis. By presenting a theoretical foundation and reference point, this review aims to contribute to both basic cell biology research and the investigation of clinically relevant diseases.

Ferroptosis in Cardiovascular Disease and Cardiomyopathies: Therapeutic Implications of Glutathione and Iron Chelating Agents

“…In the context of human pancreatic cancer cells, intriguing insights into the promotion of ferroptosis have emerged, particularly involving the endoplasmic reticulum protein stimulator of interferon genes (STING1) [ 44 ]. It has been observed that STING1 accumulates within mitochondria, where it engages with the mitochondrial outer membrane proteins mitofusins (MFN1/2) [ 44 ].…”

“…In the context of human pancreatic cancer cells, intriguing insights into the promotion of ferroptosis have emerged, particularly involving the endoplasmic reticulum protein stimulator of interferon genes (STING1) [ 44 ]. It has been observed that STING1 accumulates within mitochondria, where it engages with the mitochondrial outer membrane proteins mitofusins (MFN1/2) [ 44 ]. This interaction instigates mitochondrial fusion, leading to the generation of reactive oxygen species (ROS) and subsequent lipid peroxidation, ultimately culminating in the initiation of ferroptosis [ 44 ].…”

“…It has been observed that STING1 accumulates within mitochondria, where it engages with the mitochondrial outer membrane proteins mitofusins (MFN1/2) [ 44 ]. This interaction instigates mitochondrial fusion, leading to the generation of reactive oxygen species (ROS) and subsequent lipid peroxidation, ultimately culminating in the initiation of ferroptosis [ 44 ]. Studies employing both in vitro models and xenografted mouse experiments have highlighted the pivotal role of STING1 and MFN1/2 genes in regulating the sensitivity of pancreatic cancer cells to ferroptosis [ 45 ].…”

“…Mitochondria play a crucial protective role against ferroptosis through the regulation of Coenzyme Q (CoQ) synthesis and transport [ 44 ]. The lipid transporter StAR-related lipid transfer domain protein 7 (STARD7) is a key player in this process, being essential for both CoQ synthesis within mitochondria and its transportation to the cell membrane [ 51 ].…”

“…The lipid transporter StAR-related lipid transfer domain protein 7 (STARD7) is a key player in this process, being essential for both CoQ synthesis within mitochondria and its transportation to the cell membrane [ 51 ]. Within mitochondria, STARD7 safeguards oxidative phosphorylation and the morphogenesis of mitochondrial ridges [ 44 ]. Simultaneously, in the cytoplasm, STARD7 facilitates the transport of CoQ to the cell membrane, preventing iron oxidation.…”