Increased mitochondrial free Ca during ischemia is suppressed, but not eliminated by, germline deletion of the mitochondrial Ca uniporter.

Mitochondrial Ca overload is proposed to regulate cell death via opening of the mitochondrial permeability transition pore. It is hypothesized that inhibition of the mitochondrial Ca uniporter (MCU) will prevent Ca accumulation during ischemia/reperfusion and thereby reduce cell death. To address this, we evaluate mitochondrial Ca in ex-vivo-perfused hearts from germline MCU-knockout (KO) and wild-type (WT) mice using transmural spectroscopy.

Overexpression of a Short Sulfonylurea Splice Variant Increases Cardiac Glucose Uptake and Uncouples Mitochondria by Regulating ROMK Activity.

The mitochondrial splice variant of the sulfonylurea receptor (SUR2A-55) is associated with protection from myocardial ischemia-reperfusion (IR) injury, increased mitochondrial ATP sensitive K channel activity (mitoK) and altered glucose metabolism. While mitoK channels composed of CCDC51 and ABCB8 exist, the mitochondrial K pore regulated by SUR2A-55 is unknown. We explored whether SUR2A-55 regulates ROMK to form an alternate mitoK.

Monitoring mitochondrial calcium and metabolism in the beating MCU-KO heart.

Optical methods for measuring intracellular ions including Ca revolutionized our understanding of signal transduction. However, these methods are not extensively applied to intact organs due to issues including inner filter effects, motion, and available probes. Mitochondrial Ca is postulated to regulate cell energetics and death pathways that are best studied in an intact organ.