Recent studies report mitochondrial carrier homolog 2 (MTCH2) as a novel and 
uncharacterized protein that acts as a receptor-like protein for the truncated 
BH3-interacting domain death agonist (tBID) protein in the outer membrane of 
mitochondria. These studies, using mouse embryonic stem cells and fibroblasts as 
well as mice with a conditional knockout of MTCH2 in the liver, showed that 
deletion of MTCH2 hindered recruitment of tBID to the mitochondria with 
subsequent reductions in the activation of pro-apoptotic proteins, mitochondrial 
outer membrane permeabilization and apoptosis. Sequence analysis shows that 
MTCH2 is present in all examined multicellular Metazoa as well as unicellular 
Choanoflagellata, and is a highly derived member of the mitochondrial carrier 
family. Mitochondrial carriers are monomeric transport proteins that are usually 
found in the inner mitochondrial membrane, where they exchange small substrates 
between the mitochondrial matrix and intermembrane space. There are extensive 
differences between the protein sequences of MTCH2 and other mitochondrial 
carriers that may explain the ability of MTCH2 to associate with tBID and thus 
its role in apoptosis. We review the experimental evidence for the role of MTCH2 
in apoptosis and suggest that the original transport function of the ancestral 
MTCH2 mitochondrial carrier has been co-opted by the apoptotic machinery to 
provide a receptor and signaling mechanism.