BID, a proapoptotic BCL-2 family member, plays an essential role in the tumor 
necrosis factor alpha (TNF-alpha)/Fas death receptor pathway in vivo. Activation 
of the TNF-R1 receptor results in the cleavage of BID into truncated BID (tBID), 
which translocates to the mitochondria and induces the activation of BAX or BAK. 
In TNF-alpha-activated FL5.12 cells, tBID becomes part of a 45-kDa 
cross-linkable mitochondrial complex. Here we describe the biochemical 
purification of this complex and the identification of mitochondrial carrier 
homolog 2 (Mtch2) as part of this complex. Mtch2 is a conserved protein that is 
similar to members of the mitochondrial carrier protein family. Our studies with 
mouse liver mitochondria indicate that Mtch2 is an integral membrane protein 
exposed on the surface of mitochondria. Using blue-native gel electrophoresis we 
revealed that in viable FL5.12 cells Mtch2 resides in a protein complex of ca. 
185 kDa and that the addition of TNF-alpha to these cells leads to the 
recruitment of tBID and BAX to this complex. Importantly, this recruitment was 
partially inhibited in FL5.12 cells stably expressing BCL-X(L). These results 
implicate Mtch2 as a mitochondrial target of tBID and raise the possibility that 
the Mtch2-resident complex participates in the mitochondrial apoptotic program.