The effects of iron overload on mitochondrial function, mitochondrial dynamics, and ferroptosis in cardiomyocytes

Abstract

Excessive iron accumulation in the heart can lead to iron overload cardiomyopathy (IOC), the leading cause of death in hemochromatosis patients. Current understanding regarding the mechanism by which iron overload causes a deterioration in cardiac performance, mitochondrial dysfunction, and impaired mitochondrial dynamics remains limited. Ferroptosis, a newly identified form of regulated cell death, has recently been revealed influencing the pathophysiological process of IOC. Nevertheless, the direct effect of cardiac iron overload on ferroptotic cell death is incompletely characterized. This review article comprehensively summarizes and discusses the effects of iron overload on cardiac mitochondrial function, cardiac mitochondrial dynamics, ferroptosis of cardiomyocytes, and left ventricular function in in vitro and in vivo reports. This review also provides relevant consistent and controversial information which can facilitate further mechanistic investigation into iron-induced cardiac dysfunction in the clinical setting in the near future.

Keywords: Cell death; Ferroptosis; Heart; Iron overload; Mitochondria.