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Updated: Aug 23, 2026
Analysis of the Expression and Complexes Assembly of the Mitochondrial Respiratory Chain Proteins in the Fission Yeast Schizosaccharomyces pombe
Published on: May 2, 2025
The expression of human mitochondrial ferritin rescues respiratory function in frataxin-deficient yeast
Alessandro Campanella1, Grazia Isaya, Heather A O'Neill
1Department of Biological and Technological Research, IRCCS H San Raffaele, Via Olgettina 58, Milano, 20132 Italy.
Abstract:
Mitochondrial ferritin (MtF) is structurally and functionally similar to the cytosolic ferritins, molecules designed to store and detoxify cellular iron. MtF expression in human and mouse is restricted to the testis and few tissues, and it is abundant in the erythroblasts of patients with sideroblastic anemia, where it is thought to protect the mitochondria from the damage caused by iron loading. Mitochondria iron overload occurs also in cells deficient in frataxin, a mitochondrial protein involved in iron handling and implicated in Friedreich ataxia. We expressed human MtF in frataxin-deficient yeast cells, a well-characterized model of mitochondrial iron overload and oxidative damage. The human MtF precursor was efficiently imported by yeast mitochondria and processed to functional ferritin that actively sequestered iron in the organelle. MtF expression rescued the respiratory deficiency caused by the loss of frataxin protecting the activity of iron-sulfur enzymes and enabling frataxin-deficient cells to grow on non-fermentable carbon sources. Furthermore, MtF expression prevented the development of mitochondrial iron overload, preserved mitochondrial DNA integrity and increased cell resistance to H2O2. The data show that MtF can substitute for most frataxin functions in yeast, suggesting that frataxin is directly involved in mitochondrial iron-binding and detoxification.
Insights
Mitochondrial ferritin (MtF) can substitute for frataxin in yeast, preventing mitochondrial iron overload and protecting cells from oxidative damage. This suggests frataxin plays a key role in managing iron within mitochondria.
Area of Science:
- Biochemistry
- Cell Biology
- Genetics
Background:
- Mitochondrial ferritin (MtF) shares similarities with cytosolic ferritins, involved in iron storage and detoxification.
- MtF is found in human and mouse testes, and in erythroblasts of patients with sideroblastic anemia, protecting against iron overload.
- Mitochondrial iron overload is a hallmark of frataxin deficiency, linked to Friedreich ataxia.
Purpose of the Study:
- To investigate the potential of human MtF to counteract mitochondrial iron overload in a yeast model of frataxin deficiency.
- To assess MtF's ability to restore cellular functions impaired by frataxin loss.
Main Methods:
- Human MtF was expressed in frataxin-deficient yeast cells.
- Mitochondrial import, iron sequestration, and functional rescue were analyzed.
- Cellular respiration, iron-sulfur enzyme activity, mitochondrial DNA integrity, and oxidative stress resistance were evaluated.
Main Results:
- Human MtF was imported and processed in yeast mitochondria, actively sequestering iron.
- MtF expression rescued respiratory deficiency and enabled growth on non-fermentable carbon sources.
- MtF prevented mitochondrial iron accumulation, preserved mitochondrial DNA, and enhanced resistance to hydrogen peroxide (H2O2).
Conclusions:
- Mitochondrial ferritin (MtF) effectively substitutes for most frataxin functions in yeast.
- These findings suggest frataxin is directly involved in mitochondrial iron binding and detoxification.
- MtF shows therapeutic potential for conditions involving mitochondrial iron overload.
