Biology of the Mitochondrial Contact Site and Cristae Organizing System in Trypanosomatids

This study describes Mitochondrial Contact Site and Cristae Organizing System (MICOS) in unicellular parasitic protist Trypanosoma brucei. This is the first study of MICOS outside of canonical model organisms belonging to the supergroup Opisthokonta. Nine subunits of the complex were purified and characterized. Their role in cristae biogenesis and interaction with other mitochondrial protein complexes was demonstrated. Further investigation revealed a hierarchical organization of T. brucei MICOS and the existence of two subcomplexes. One of MICOS subunits, TbMic20, facilitates protein import into mitochondrial intermembrane space, which is one of the novel features of T. brucei MICOS. The role of TbMic20 in oxidative protein folding was demonstrated and the mechanism of this process in T. brucei was addressed

The highly diverged trypanosomal MICOS complex is organized in a non‐essential integral membrane and an essential peripheral module

The mitochondrial contact site and cristae organization system (MICOS) mediates the formation of cristae, invaginations in the mitochondrial inner membrane. The highly diverged MICOS complex of the parasitic protist Trypanosoma brucei consists of 9 subunits. Except for two Mic10-like and a Mic60-like protein, all subunits are specific for kinetoplastids. Here we determined on a proteome-wide scale how ablation of individual MICOS subunits affects the levels of the other subunits. The results reveal co-regulation of TbMic10-1, TbMic10-2, TbMic16 and TbMic60, suggesting that these non-essential, integral inner membrane proteins form an interdependent network. Moreover, the ablation of TbMic34 and TbMic32 reveals another network consisting of the essential, intermembrane space-localized TbMic20, TbMic32, TbMic34 and TbMic40, all of which are peripherally associated with the inner membrane. The downregulation of TbMic20, TbMic32 and TbMic34 also interferes with mitochondrial protein import and reduces the size of the TbMic10-containing complexes. Thus, the diverged MICOS of trypanosomes contains two subcomplexes: a non-essential membrane-integrated one, organized around the conserved Mic10 and Mic60, that mediates cristae formation, and an essential membrane-peripheral one consisting of four kinetoplastid-specific subunits, that is required for import of intermembrane space proteins