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

Kód výsledku v 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>

Nalezeny alternativní kódy

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

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Current Biology

ISSN

0960-9822

e-ISSN

1879-0445

Svazek periodika

35

Číslo periodika v rámci svazku

23

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

15

Strana od-do

5734-5749

Kód UT WoS článku

001633433800001

EID výsledku v databázi Scopus

2-s2.0-105023513225