A human mitochondrial ferritin encoded by an intronless gene
Open accessAbstract
Ferritin is a ubiquitous protein that plays a critical role in regulating intracellular iron homoeostasis by storing iron inside its multimeric shell. It also plays an important role in detoxifying potentially harmful free ferrous iron to the less soluble ferric iron by virtue of the ferroxidase activity of the H subunit. Although excess iron is stored primarily in cytoplasm, most of the metabolically active iron in cells is processed in mitochondria. Little is yet known of how these organelles regulate iron homeostasis and toxicity. Here we report an unusual intronless gene on chromosome 5q23.1 that encodes a 242-amino acid precursor of a ferritin H-like protein. This 30-kDa protein is targeted to mitochondria and processed to a 22-kDa subunit that assembles into typical ferritin shells and has ferroxidase activity. Immunohistochemical analysis showed that it accumulates in high amounts in iron-loaded mitochondria of erythroblasts of subjects with impaired heme synthesis. This new ferritin may play an important role in the regulation of mitochondrial iron homeostasis and heme synthesis.
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A mitochondrial form of ferritin exists which may protect mitochondria against iron-mediated toxicity and provide a quick source of iron.
“There also exists a mitochondrial form of ferritin (Levi et al., 2001) which may both protect mitochondria against iron-mediated toxicity and provide a quick and efficient source of iron in this organelle rather than relying solely on the cytosolic ferritin.”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Levi et al., 2001
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- Authors
- Levi, S., Corsi, B., Bosisio, M., Invernizzi, R., Volz, A., Sanford, D., Arosio, P., & Drysdale, J.
- Affiliations
- IRCCS Ospedale San Raffaele (IT)
- University of Brescia (IT)
- University of Pavia (IT)
- Humboldt-Universität zu Berlin (DE)
- Tufts University (US)
- Corresponding author
- Drysdale, Jim
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-01
- Volume
- 276
- Issue
- 27
- Pages
- 24437-24440
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2006383772
- Cited by
- 400
- References
- 26
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 17 · 2023: 12 · 2022: 18 · 2021: 19 · 2020: 13 · 2019: 14 · 2018: 13 · 2017: 22 · 2016: 19 · 2015: 10 · 2014: 15 · 2013: 18 · 2012: 11
- FWCI
- 8.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Funders
- Tufts University School of Medicine
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- mitochondrial ferritin, intronless genes, iron homeostasis, ferroxidase activity, mitochondrial iron, heme biosynthesis, erythroblasts, iron overload
- MeSH terms
- Amino Acid Sequence, Anemia, Sideroblastic, Animals, Ceruloplasmin, Chromosomes, Human, Pair 5, Erythroblasts, Ferritins, HeLa Cells, Heme, Humans, Immunohistochemistry, Introns, Iron, Mitochondria, Molecular Sequence Data, Molecular Weight, Restriction Mapping, Sequence Alignment, Mice
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