The regulation of mitochondrial ferritin on mitochondrial redox balance is essential to cell fate decision

TL;DR

Mitochondrial ferritin helps control iron levels in mitochondria, which affects cell survival and disease, offering new treatment possibilities.

Contribution

Highlights FtMt's unique role in mitochondrial redox balance and its implications for cell fate and disease.

Findings

FtMt isolates iron in mitochondria, reducing oxidative stress and maintaining redox balance.

FtMt influences cell fate decisions through regulation of mitochondrial integrity and redox homeostasis.

Dysregulation of FtMt is linked to neurodegenerative diseases, cardiovascular disorders, and aging-related conditions.

Abstract

Mitochondrial ferritin (FtMt), first identified by Levi et al., is an iron-storage protein with high homology with cytoplasmic ferritin. It is mainly expressed in metabolically active tissues and exhibits distinct physiological and biochemical properties compared cytoplasmic ferritin. Over the past few decades, significant attention has been drawn to the unique structural and functional characteristics of FtMt that differentiates it from conventional ferritin. Mitochondrial ferritin specifically located on the mitochondrial exhibits unique advantages in mitochondrial redox balance through isolating iron within mitochondria, reducing oxidative stress and maintaining mitochondrial homeostasis. Moreover, it modulates the labile iron pool within mitochondria, facilitating the biosynthesis of iron-sulfur clusters and supporting cellular respiration. This review comprehensively discusses the pivotal function of FtMt in regulating mitochondrial redox homeostasis and its impact on cell fate decisions, specifically, its influence on apoptosis, ferroptosis through alterations in mitochondrial integrity. We also summarize recent advances in understanding the association between FtMt dysregulation and various diseases, emphasizing its implications in neurodegenerative diseases, cardiovascular disorders and cerebrovascular pathologies. By critically evaluating emerging evidence, this article aims to provide translational insights into targeting FtMt and mitochondrial redox homeostasis as therapeutic strategies for mitigating these clinically significant diseases.

•Mitochondrial ferritin (FtMt) can isolate free iron in mitochondria and participate in the regulation of mitochondrial redox balance.•FtMt participates in cellular energy generation and mitophagy processes.•FtMt participates in cell fate determination by regulating cellular redox balance.•FtMt plays an important protective role in various neurodegenerative, tumor, and aging-related diseases.•FtMt provides new therapeutic strategies for maintaining redox balance and disease intervention.

Mitochondrial ferritin (FtMt) can isolate free iron in mitochondria and participate in the regulation of mitochondrial redox balance.

FtMt participates in cellular energy generation and mitophagy processes.

FtMt participates in cell fate determination by regulating cellular redox balance.

FtMt plays an important protective role in various neurodegenerative, tumor, and aging-related diseases.

FtMt provides new therapeutic strategies for maintaining redox balance and disease intervention.

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