The Diverged Trypanosome MICOS Complex as a Hub for Mitochondrial Cristae Shaping and Protein Import

Abstract

Graphical Abstract Highlights d First study of MICOS outside opisthokonts verifies a conserved role in shaping cristae d Trypanosome MICOS novelties include two distinct Mic10s and an atypical Mic60 d TbMICOS features a novel thioredoxin-like subunit called TbMic20 d TbMic20 appears to be a catalyst for intermembrane space protein import

Cell Biology: Functional Conservation, Structural Divergence, and Surprising Convergence in the MICOS Complex of Trypanosomes

“…Despite being considerably divergent in composition and structure, TbMICOS appears to be functionally conserved. Kaurov et al [2] show that TbMICOS is associated with crista membranes, and disruption of some subunits (but not others) leads to elongated cristae and apparent loss of crista junctions, in agreement with what has been seen in fungi and animals [5,14]. Furthermore, TbMICOS interacts with the sorting and assembly machinery (SAM) complex and therefore The MICOS complex has now been experimentally well characterized in three different lineages from disparate branches of the eukaryote tree.…”

“…But this is not the only unusual feature of trypanosomatids and their mitochondria. In this issue of Current Biology, Hashimi and colleagues [2] experimentally characterize the functionally conserved but structurally divergent mitochondrial contact site and cristae organizing system (MICOS) complex in T. brucei and uncover a surprising convergence along the way.…”

“…The apparent lack of both Mic60 and Mia40 in trypanosomes was puzzling. By experimentally characterizing the MICOS complex of T. brucei (TbMICOS), Kaurov et al [2] now provide tentative answers to this intriguing mystery. Using multiple methods, they identify at least nine TbMICOS subunits and biochemically distinguish membranebound from peripheral subunits.…”

“…The really big surprise uncovered by Kaurov et al [2] was the discovery of a putative alternative mechanism for protein import into the mitochondrial intermembrane space. In most other aerobic eukaryotes, Mia40 plays a major role in the import and oxidative folding of intermembrane-space proteins with CX 3 C and CX 9 C motifs [13].…”

“…In yeast, Mia40 interaction with MICOS is important for efficient import of these intermembrane-space proteins [4]. Kaurov et al [2] show that depletion of the thioredoxin-like TbMic20 subunit correlates with a reduction in the steadystate levels of many intermembranespace proteins, specifically several proteins containing CX 3 C and CX 9 C motifs. This observation led them to suggest that TbMic20 is a functional analogue of Mia40.…”