Non-transferrin-bound iron uptake by cardiomyocytes

Under conditions of iron overload, increased non-transferrin-bound iron (NTBI) can gain access to cardiomyocytes, cause cardiac iron accumulation and generate reactive oxygen species which can result in iron-overload cardiomyopathy. Currently, it is not fully understood how cardiomyocytes take up NTBI under iron-overload conditions. However, the large number of studies conducted over the past few decades have greatly improved our understanding of this critical issue in the field of heart disease, but so far there has been no effort to synthesize these studies and isolated ideas into a systematic and coherent summary. Herein, we focus on up-to-date advances in studies on the routes for cardiomyocytes to uptake NTBI, including L-type Ca2 + channels (LTCC), T-type Ca2 + channels (TTCC), divalent metal transporter 1 (DMT1), the Lipocalin-2 (LCN-2) / Lipocalin-2 receptor (LCN-2R) system and ZIP14 (SLC39A14). We also offer suggestions for addressing some critical gaps still extant in our understanding of this important topic.