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

FEBS Letters

article

Ola Karmi¹  Linda Rowland¹  Skylar D. King¹  Camila Manrique-Acevedo³  Ioav Z. Cabantchik²  Rachel Nechushtai²  Ron Mittler¹ 

[1] Department of Surgery, University of Missouri School of Medicine, Christopher S. Bond Life Sciences Center, University of Missouri;The Alexander Silberman Institute of Life Science, The Hebrew University of Jerusalem;Dalton Cardiovascular Research Center, University of Missouri;Division of Endocrinology and Metabolism, Department of Medicine, University of Missouri;Harry S. Truman Memorial Veterans' Hospital;The Division of Plant Sciences and Interdisciplinary Plant Group, College of Agriculture, Food and Natural Resources, Christopher S. Bond Life Sciences Center, University of Missouri

关键词: cardiomyocytes;    CISD2;    iron;    knockout mice;    mitochondria;    reactive oxygen species;   

DOI  :  10.1002/1873-3468.14277

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown