The essential cysteines in the CIPC motif of the thioredoxin-like Trypanosoma brucei MICOS subunit TbMic20 do not form an intramolecular disulfide bridge in vivo

0557404 - BC 2023 RIV NL eng J - Journal Article
Kaurov, Iosif - Heller, Jiří - Deisenhammer, S. - Potěšil, D. - Zdráhal, Z. - Hashimi, Hassan
The essential cysteines in the CIPC motif of the thioredoxin-like Trypanosoma brucei MICOS subunit TbMic20 do not form an intramolecular disulfide bridge in vivo.
Molecular and Biochemical Parasitology. Roč. 248, MAR (2022), č. článku 111463. ISSN 0166-6851. E-ISSN 1872-9428
R&D Projects: GA ČR(CZ) GA20-23513S; GA MŠMT(CZ) EF16_019/0000759
Institutional support: RVO:60077344
Keywords : intermembrane space * bond formation * mia pathway * redox properties * protein import * relay system * mitochondrial * identification * evolution * oxidoreductase * Trypanosoma * Mitochondrion * micos * Protein import * Intermembrane space * Oxidative folding
OECD category: Cell biology
Impact factor: 1.5, year: 2022
Method of publishing: Open access
https://www.sciencedirect.com/science/article/pii/S0166685122000172?via%3Dihub

The mitochondrial protein import machinery of trypanosomatids is highly divergent from that of the well-studied models such as baker's yeast. A notable example is that the central catalyst of the mitochondrial intermembrane space import and assembly pathway (MIA), named Mia40, is missing in trypanosomatids. Mia40 works in a two-step process. First it recognizes by direct binding reduced MIA substrate proteins and then catalyzes their oxidative folding to produce intramolecular disulfide bridges. It was recently proposed that a thioredoxin-like subunit of the trypanosomal mitochondrial contact site and cristae organizing system (MICOS) called TbMic20 may be the Mia40 replacement. Our study performed on procyclic stage of the parasite revealed that each of the two cysteines in TbMic20's active site is essential for the stability of MIA substrate proteins although they do not form a disulfide bridge in vivo. The two cysteines of Mia40 & PRIME,s active site form an intramolecular di-sulfide bridge at steady state, which is a prerequisite for its oxidative folding of MIA substrates. Thus, we conclude that TbMic20 is unlikely to represent a bona fide Mia40 replacement and plays a still unresolved role in the stability and/or import of MIA substrates in trypanosomatids. Despite this, the effect of TbMic20 depletion and mutation indicates that the trypanosomal MICOS complex still plays a vital role in the maturation and/or stability of proteins imported by the MIA pathway.
Permanent Link: https://hdl.handle.net/11104/0339355