Informace o publikaci

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

Autoři	KAUROV Iosif HELLER Jiří DEISENHAMMER Sebastian POTĚŠIL David ZDRÁHAL Zbyněk HASHIMI Hassan
Rok publikování	2022
Druh	Článek v odborném periodiku
Časopis / Zdroj	MOLECULAR AND BIOCHEMICAL PARASITOLOGY
Fakulta / Pracoviště MU	Středoevropský technologický institut
Citace
www	fulltext
Doi	http://dx.doi.org/10.1016/j.molbiopara.2022.111463
Klíčová slova	Trypanosoma Mitochondrion MICOS Protein import Intermembrane space Oxidative folding
Popis	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.