Mitochondrial Creatine Kinase Counters ROS Emission in Failing Hearts

The failing heart is energy-starved and redox imbalanced. Understanding how, and where cardiac energetic and redox alterations intersect in the failing heart are paramount to understanding and treating heart failure (HF). Creatine kinase (CK) is the major myocardial energy reserve reaction and ATP buffer with isozymes in the cytosol (CK-M) and mitochondria (Mt-CK). CK activity is reduced in human HF and following transverse aortic constriction (TAC). Mt-CK is an octamer particularly prone to oxidative modifications. It is not known whether HF changes in Mt-CK contribute to alter myocardial redox state in HF. We found that, in failing TAC WT hearts, a marked rise in reactive oxygen species (ROS) emission occurs (+93%, n=13, p