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

J 2022

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

KAUROV, Iosif, Jiří HELLER, Sebastian DEISENHAMMER, David POTĚŠIL, Zbyněk ZDRÁHAL et. al.

Basic information

Original name

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

Authors

KAUROV, Iosif (203 Czech Republic), Jiří HELLER (203 Czech Republic), Sebastian DEISENHAMMER (203 Czech Republic), David POTĚŠIL (203 Czech Republic, belonging to the institution), Zbyněk ZDRÁHAL (203 Czech Republic, guarantor, belonging to the institution) and Hassan HASHIMI (203 Czech Republic)

Edition

MOLECULAR AND BIOCHEMICAL PARASITOLOGY, NETHERLANDS, ELSEVIER, 2022, 0166-6851

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

fulltext

Impact factor

Impact factor: 1.500

RIV identification code

RIV/00216224:14740/22:00125952

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1016/j.molbiopara.2022.111463

UT WoS

000787886300003

Keywords in English

Trypanosoma Mitochondrion MICOS Protein import Intermembrane space Oxidative folding

Abstract

V originále

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.

Links

90127, large research infrastructures

Name: CIISB II

Citovat

KAUROV, Iosif, Jiří HELLER, Sebastian DEISENHAMMER, David POTĚŠIL, Zbyněk ZDRÁHAL and Hassan HASHIMI. 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. NETHERLANDS: ELSEVIER, 2022, vol. 248, MAR, p. "111463", 10 pp. ISSN 0166-6851. Available from: https://dx.doi.org/10.1016/j.molbiopara.2022.111463.

@article{1858757,
   author = {Kaurov, Iosif and Heller, Jiří and Deisenhammer, Sebastian and Potěšil, David and Zdráhal, Zbyněk and Hashimi, Hassan},
   article_location = {NETHERLANDS},
   article_number = {MAR},
   doi = {http://dx.doi.org/10.1016/j.molbiopara.2022.111463},
   keywords = {Trypanosoma Mitochondrion MICOS Protein import Intermembrane space Oxidative folding},
   language = {eng},
   issn = {0166-6851},
   journal = {MOLECULAR AND BIOCHEMICAL PARASITOLOGY},
   title = {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},
   url = {http://www.sciencedirect.com/science/article/pii/S0166685122000172},
   volume = {248},
   year = {2022}
}

TY  - JOUR
ID  - 1858757
AU  - Kaurov, Iosif - Heller, Jiří - Deisenhammer, Sebastian - Potěšil, David - Zdráhal, Zbyněk - Hashimi, Hassan
PY  - 2022
TI  - 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
JF  - MOLECULAR AND BIOCHEMICAL PARASITOLOGY
VL  - 248
IS  - MAR
SP  - "111463"
EP  - "111463"
PB  - ELSEVIER
SN  - 01666851
KW  - Trypanosoma Mitochondrion MICOS Protein import Intermembrane space Oxidative folding
UR  - http://www.sciencedirect.com/science/article/pii/S0166685122000172
N2  - 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.
ER  -

KAUROV, Iosif, Jiří HELLER, Sebastian DEISENHAMMER, David POTĚŠIL, Zbyněk ZDRÁHAL and Hassan HASHIMI. 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. \textit{MOLECULAR AND BIOCHEMICAL PARASITOLOGY}. NETHERLANDS: ELSEVIER, 2022, vol.~248, MAR, p.~''111463'', 10 pp. ISSN~0166-6851. Available from: https://dx.doi.org/10.1016/j.molbiopara.2022.111463.

Detailed Information on Publication Record