Authors

Discussion

Invaginations of the inner mitochondrial membrane, so-called cristae, come in a variety of shapes and forms. They compartmentalise electron transport chain complexes, confined by diffusion barriers called cristae junctions (CJ), thus making them vitally important for efficient energy generation in mitochondria. The mitochondrial contact site and cristae organising complex (MICOS), found at these CJs, plays a role in crista formation and providing contact sites between inner and outer membrane through interaction with outer membrane protein Sam50.

While the mammalian bloodstream form (BSF) of the Trypanosoma brucei parasite has a tubular mitochondrion with tiny, stub-like cristae the insect procyclic form (PCF) possesses an elaborately branched, reticulated organelle with fully developed discoidal cristae harbouring electron transport chain complexes. Differentiation between these two life cycle stages can be induced in vitro, thus making the parasite an ideal model system to study cristae development. T. brucei MICOS consists of nine proteins and forms two subcomplexes which differ in their localisation and function in the PCF. The membrane-embedded integral subcomplex of MICOS is important for CJ formation and maintaining cristae shape while the peripheral complex seems to be essential for import of intermembrane space proteins by an oxidative folding pathway.

We show here that the core subunits of MICOS as well as interactions with SAM50 and ATP synthase are conserved in the BSF. Interestingly, four novel interactors were also discovered perhaps indicating additional or divergent functions of MICOS in this life cycle stage. Consistent with this notion, and in contrast to the situation in the PCF, gene deletion mutants of peripheral subcomplex subunits are viable in the BSF. Furthermore, the conserved trypanosome Mic10 homolog, which is part of the integral subcomplex, is also dispensable for differentiation to the PCF.

In contrast, the absence of peripheral trypanosome-specific MICOS components Mic34 or Mic40 compromises differentiation and mitochondrial morphology, correlated with defective electron transport chain complex assembly. This is most likely due to the two proteins’ central yet still undefined role in protein import in the PCF life stage. This interdependency between mitochondrial protein import and morphology is also exemplified by the effects of RNAi-mediated depletion of Mic34 and Mic40 in the PCF. The highly branched mitochondrion normally found in this life cycle stage is rendered more simplistic and tubular like its BSF equivalent when Mic34 or Mic40 levels are reduced. This clear division of labour between the two trypanosome MICOS subcomplexes, with the peripheral one being vital for the stability of proteins imported into the intermembrane space, and the dispensability of the Mic10 homolog sets T. brucei MICOS apart from its opisthokont (e.g. yeast and animal) counterpart.