Is MCU dispensable for normal heart function?

Abstract

The uptake of Ca²⁺ into mitochondria is thought to be an important signal communicating the need for increased energy production. However, dysregulated uptake leading to mitochondrial Ca²⁺ overload can trigger opening of the mitochondrial permeability transition pore and potentially cell death. Thus mitochondrial Ca²⁺ entry is regulated via the activity of a Ca²⁺-selective channel known as the mitochondrial calcium uniporter. The last decade has seen enormous momentum in the discovery of the molecular identities of the multiple proteins comprising the uniporter. Increasing numbers of studies in cultured cells and animal models have provided insight into how disruption of uniporter proteins affects mitochondrial Ca²⁺ regulation and impacts tissue function and physiology. This review aims to summarize some of these recent findings, particularly in the context of the heart.