Activity of the mitochondrial calcium uniporter varies greatly between tissues

Abstract

The mitochondrial calcium uniporter (MCU) is a highly selective channel responsible for mitochondrial Ca2+ uptake. The MCU shapes cytosolic Ca2+ signals, controls mitochondrial ATP production, and is involved in cell death. Here, using direct patch-clamp recording from the inner mitochondrial membrane, we compare MCU activity in mouse heart, skeletal muscle, liver, kidney, and brown fat. Surprisingly, heart mitochondria shows a dramatically lower MCU current density than the other tissues studied. Similarly, in Drosophila flight muscle, MCU activity is barely detectable compared to that in other fly tissues. Because mitochondria occupy up to 40% of the cell volume in highly metabolically active heart and flight muscle, low MCU activity is likely essential to avoid cytosolic Ca2+ sink due to excessive mitochondrial Ca2+ uptake. Simultaneously, low MCU activity may also prevent mitochondrial Ca2+ overload in such active tissues exposed to frequent cytosolic Ca2+ activity.