The [2Fe-2S] protein CISD2 plays a key role in preventing iron accumulation in cardiomyocytes

Ola Karmi, Linda Rowland, Skylar D. King, Camila Manrique-Acevedo, Ioav Z. Cabantchik, Rachel Nechushtai, Ron Mittler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Considered a key aging gene, CISD2, encoding CDGSH iron–sulfur domain-containing protein 2, plays a central role in regulating calcium homeostasis, preventing mitochondrial dysfunction, and the activation of autophagy and apoptosis in different cells. Here, we show that cardiomyocytes from CISD2-null mice accumulate high levels of iron and contain high levels of transferrin receptor and ferritin. Using proteomics and transmission electron microscopy, we further show that the lack of CISD2 induces several features of the aging process in young mice, but other features are not induced. Taken together, our findings suggest that CISD2 protects cardiomyocytes from overaccumulation of iron, which is common in aging hearts and can contribute to the pathogenesis of heart failure.

Original languageAmerican English
Pages (from-to)747-761
Number of pages15
JournalFEBS Letters
Issue number6
Early online date8 Jan 2022
StatePublished - Mar 2022

Bibliographical note

Publisher Copyright:
© 2022 Federation of European Biochemical Societies.


  • CISD2
  • cardiomyocytes
  • iron
  • knockout mice
  • mitochondria
  • reactive oxygen species


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