The ubiquitin proteasome system plays a role in regulating protein activity and is integral to the turnover of damaged and worn proteins. In this review, we discuss the recently described relationship between the ubiquitin proteasome system and the cardiac creatine kinase/phospho-creatine shuttle, an essential component of ATP generation and energy shuttling within the heart. The ubiquitin ligase muscle ring finger-1 (MuRF1) binds creatine kinase, leading to its ubiquitination and possible degradation. MuRF1 may also be integral in the regulation of creatine kinase activity in vivo. Since there is a close relationship between the cardiac creatine kinase/phospho-creatine shuttle activity and heart failure, these findings suggest that MuRF1’s role in protein quality control of creatine kinase may be vital to the regulation and maintenance of cardiac energetics to protect against heart failure
