UCPs - unlikely calcium porters

The mitochondrial Ca2+ uniporter (MCU) has been characterized for several decades, but the molecule responsible for this transport activity is currently unknown. Therefore, a recent Nature Cell Biology paper by Trenker et al. reporting a role for uncoupling proteins (UCP2/3) in mitochondrial Ca2+ uniport generated much excitement in the field. Subsequently, the authors contend that Ca2+ transport accounts for most of the physiological effects assigned to UCPs3. In this experimental Correspondence we address our concerns about the results of Trekner et al (Nature Cell Biol 9, 445–452, 2007). Taking our results together with concerns over the appropriateness of tissues chosen for UCP genetic ablation experiments, and observations on free [Ca2+]m that are incompatible with established knowledge about mitochondrial Ca2+ transport, we suggest that the results of Trenker et al. be regarded with caution. It is currently premature to assign any role in mitochondrial Ca2+ uniport to UCPs.