Page 11 - GTM-3-2

Global Translational Medicine

REVIEW ARTICLE
Mitochondrial involvement in ferroptotic cell

death

1,2
1
Chayan Munshi *, Tithi Paul , Kalpesh Jas 1,2† , Mihieka Bose 1,2† , and Shelley
Bhattacharya 2
1 Ethophilia Research Foundation, Santiniketan, India
2 Department of Zoology, Visva Bharati University, Santiniketan, India

Abstract
Ferroptosis is a regulated cell death pathophysiologically associated with the
depletion of the antioxidant system due to iron overload, which results in excess
lipid peroxidation. Mitochondria are crucial organelles known for their prominent
involvement in various cellular metabolic activities and cell death processes. While our
understanding of ferroptotic signaling pathways is advancing, further investigation
into the intricate relationship between mitochondrial bio-process and this mode of
cell death is necessary to identify effective biomedical therapeutic options targeting
this organelle. However, the direct involvement of mitochondria in ferroptosis has
remained a topic of debate due to the limited availability of concrete information
to date. This review aims to elucidate the pathophysiological perspectives of
mitochondria during ferroptotic cell death.

† These authors contributed equally Keywords: Ferroptosis; Mitochondria; Cell death
to this work.
*Corresponding author:
Chayan Munshi
(chayanbio@gmail.com) 1. Introduction
Citation: Munshi C, Paul T, Ferroptosis is a regulated form of cell death characterized by iron-dependent
Jas K, Bose M, Bhattacharya
S. Mitochondrial involvement in lipid peroxidation and oxidative damage, which eventually triggers the loss of
ferroptotic cell death. Global Transl membrane integrity and the release of molecules associated with cellular damage.
Med. 2024;3(2):2208. Iron overload (alteration in iron homeostasis) plays a crucial role in generating
https://doi.org/10.36922/gtm.2208
reactive oxygen species (ROS) and promoting lipid peroxidation. The delicate
Received: November 8, 2023 balance of iron homeostasis, regulated by translational and transcriptional
Accepted: January 4, 2024
Published Online: March 18, 2024 mechanisms, determines the susceptibility to ferroptosis, which leads to various
1
Copyright: © 2024 Author(s). pathologies, such as neurological disorders and ischemia-reperfusion injury. A
This is an Open-Access article thorough understanding of the molecular mechanisms underlying iron metabolism
distributed under the terms of the during ferroptotic cell death may pave the way for effective therapeutic strategies
Creative Commons Attribution
License, permitting distribution, for these diseases. Notably, iron chelators have demonstrated significant efficacy
and reproduction in any medium, in preventing ferroptosis, providing novel therapeutic approaches for iron-related
provided the original work is 2
properly cited. pathophysiological conditions.
Publisher’s Note: AccScience Ferroptosis is a type of iron-mediated, non-apoptotic regulated cell death.
Publishing remains neutral with Mechanistically, iron accumulation, increased lipid peroxidation, and the inability to
regard to jurisdictional claims in
published maps and institutional efficiently diminish lipid peroxidation are the main drivers of ferroptosis. While iron
affiliations. is essential for oxygen transport through hemoglobin and various metabolic pathways,

Volume 3 Issue 2 (2024) 1 https://doi.org/10.36922/gtm.2208