Activity of the mitochondrial calcium uniporter varies greatly between tissues

Abstract

The mitochondrial calcium uniporter is a highly selective channel responsible for mitochondrial Ca2+ uptake. The mitochondrial calcium uniporter 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 mitochondrial calcium uniporter activity in mouse heart, skeletal muscle, liver, kidney and brown fat. Surprisingly, heart mitochondria show a dramatically lower mitochondrial calcium uniporter current density than the other tissues studied. Similarly, in Drosophila flight muscle, mitochondrial calcium uniporter activity is barely detectable compared with that in other fly tissues. As mitochondria occupy up to 40% of the cell volume in highly metabolically active heart and flight muscle, low mitochondrial calcium uniporter activity is likely essential to avoid cytosolic Ca2+ sink due to excessive mitochondrial Ca2+ uptake. Simultaneously, low mitochondrial calcium uniporter activity may also prevent mitochondrial Ca2+ overload in such active tissues exposed to frequent cytosolic Ca2+ activity. The flow of calcium into the mitochondrial matrix is mediated by the mitochondrial calcium uniporter. Fieniet al. apply patch-clamp techniques to mitoplasts isolated from different mouse and Drosophilatissues and find that the mitochondrial calcium uniporter activity varies depending on the tissue studied.