Response to Zarsky et al. [Letter to the Editor]

Mitochondria evolved from an alpha-proteobacterial endosymbiont and recent phylogenetic and function-based research has demonstrated that the major pieces of the protein transport machinery were inherited from the symbiont. This includes the SAM machinery for assembly of outer membrane proteins and the TIM machinery for protein transport across, and assembly into, the mitochondrial inner membrane [1-3]. Hidden Markov model (HMM) analysis, which enables a broad, all-encompassing approach for identifying protein homologies, has been very important in detecting members of protein families that are not easily recognized by simple BLAST-based comparisons [1]; HMM searches initially failed to find a Tom40 protein in one group of eukaryotes, the kinetoplastids. These organisms, which include the experimentally-tractable Trypanosoma brucei, have highly developed mitochondria that have evolved from the same ancestor as mitochondria in other eukaryotes. The initial failure to identify a Tom40 homolog in T. brucei was both surprising and exciting.