Characterization of the sTim/MIA pathway in Metamonada reveals different evolutionary adaptations to anaerobiosis

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F25%3A00645060" target="_blank" >RIV/60077344:_____/25:00645060 - isvavai.cz</a>

Alternative codes found

RIV/68378050:_____/25:00645060 RIV/00216208:11310/25:10505863

Result on the web

<a href="https://doi.org/10.1016/j.cub.2025.10.027" target="_blank" >https://doi.org/10.1016/j.cub.2025.10.027</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.cub.2025.10.027" target="_blank" >10.1016/j.cub.2025.10.027</a>

Result language

angličtina

Original language name

Characterization of the sTim/MIA pathway in Metamonada reveals different evolutionary adaptations to anaerobiosis

Original language description

Adaptation of eukaryotic cells to oxygen-poor environments has driven metabolic changes in mitochondria, notably shifting from oxygen-dependent to anaerobic energy metabolism. However, how the mitochondrial protein import machinery adapts in anaerobes remains poorly understood, although oxygen is crucial for this process, particularly for oxidative folding of small Tim (sTim) chaperones. sTim heterohexameric complexes guide imported proteins within the mitochondrial intermembrane space (IMS). Their function depends on conserved twin cysteines, oxidized by the mitochondrial import and assembly (MIA) pathway to stabilize their structure via disulfide bridges. The folding requires molecular oxygen or cytochrome c as electron acceptors, linking sTim folding to respiration. This study elucidates how the sTim/MIA pathway is reshaped in anaerobic types of mitochondria, such as hydrogenosomes. Through structural and homology analyses across anaerobic eukaryotes, three modifications of the sTim/MIA system were identified: (1) a disulfide relay-independent system with sTims lacking twin cysteines (sTim−cys), (2) absence of sTim/MIA components, and (3) a conventional sTim/MIA system linked to fumarate reduction. The sTim−cys system found in Metamonada was studied in Trichomonas vaginalis hydrogenosomes. Structural modeling, in vitro, and in situ analyses revealed that despite lacking canonical cysteines, sTim−cys proteins maintain the helix-loop-helix architecture with the central loop involved in targeting to the IMS and assemble into complexes stabilized by electrostatic interactions. Single-particle analysis confirmed their 6-fold symmetry, similar to conventional sTim heterohexamers. These findings provide insights into the evolutionary shaping of sTim/MIA pathways in anoxic environments, contributing to our understanding of mitochondrial biogenesis across diverse eukaryotes.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10601 - Cell biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Current Biology

ISSN

0960-9822

e-ISSN

1879-0445

Volume of the periodical

35

Issue of the periodical within the volume

23

Country of publishing house

US - UNITED STATES

Number of pages

15

Pages from-to

5734-5749

UT code for WoS article

001633433800001

EID of the result in the Scopus database

2-s2.0-105023513225