Mitochondrial Iron Metabolism and Homeostasis

Mitochondria lie at the heart of cellular iron metabolism, serving both as the principal site for heme and iron–sulfur cluster synthesis and as a dynamic reservoir for labile iron. Iron enters the organelle via dedicated carrier proteins, is incorporated into prosthetic groups essential for respiratory chain complexes and numerous metabolic enzymes, and is safely stored or exported to maintain redox balance. Mitochondrial ferritin sequesters excess iron to limit free radical formation, while chaperones and carriers regulate delivery to biosynthetic pathways. Disruption of these processes leads to impaired energy production, heightened oxidative stress and cell death pathways such as ferroptosis. Given the universal requirement for iron in both normal physiology and pathological states—from neurodegeneration to cardiomyopathy—understanding how mitochondria acquire, utilise, store and export iron is crucial to devising therapies that restore cellular homeostasis and protect against iron-driven damage.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Mitochondrial Iron Metabolism and Homeostasis publication trend

The graph below shows the total number of articles in mitochondrial iron metabolism and homeostasis across all publications each year (not limited to Nature Index journals).

Technical terms

Ferroptosis: regulated form of cell death precipitated by iron-dependent peroxidation of membrane lipids.

Mitochondrial ferritin (FtMt): an iron-storage protein within the mitochondrial matrix that sequesters excess iron and guards against oxidative stress.

Labile iron pool: the readily exchangeable fraction of cellular iron that feeds biosynthetic pathways and can catalyse free radical generation when unshielded.

Iron–sulfur cluster: a covalently assembled cofactor composed of iron and inorganic sulfur atoms, critical for electron transfer and enzyme catalysis.

Mitochondrial carrier family (Mrs3/4p): inner-membrane transport proteins responsible for importing iron into the mitochondrial matrix, especially under low-iron conditions.

References

1. The crosstalk between mitochondrial quality control and metal-dependent cell death. Cell Death & Disease (2024).
2. A Human Mitochondrial Ferritin Encoded by an Intronless Gene*. Journal of Biological Chemistry (2001).
3. A Specific Role of the Yeast Mitochondrial Carriers Mrs3/4p in Mitochondrial Iron Acquisition under Iron-limiting Conditions*. Journal of Biological Chemistry (2003).