Mitochondrial Ca2+ in heart failure: Not enough or too much?

Ca2+ serves as a ubiquitous second messenger mediating a variety of cellular processes including electrical excitation, contraction, gene expression, secretion, cell death and others. The identification of the molecular components of the mitochondrial Ca2+ influx and efflux pathways has created a resurgent interest in the regulation of mitochondrial Ca2+ balance and its physiological and pathophysiological roles. While the pace of discovery has quickened with the availability of new cellular and animal models, many fundamental questions remain to be answered regarding the regulation and functional impact of mitochondrial Ca2+ in health and disease. This review highlights several experimental observations pertaining to key aspects of mitochondrial Ca2+ homeostasis that remain enigmatic, particularly whether mitochondrial Ca2+ signaling is depressed or excessive in heart failure, which will determine the optimal approach to therapeutic intervention.

Automated summary

The discovery of mitochondrial Ca2+ influx and efflux pathways has reignited interest in the regulation of mitochondrial Ca2+ balance and its roles in health and disease. Despite advances in cellular and animal models, fundamental questions remain about the regulation and functional impact of mitochondrial Ca2+, particularly in heart failure, which will impact therapeutic approaches.