The Core MICOS Complex Subunit mic60 has Been Substituted by Two Cryptic Mitofilin-containing Proteins in Euglenozoa

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F25%3A00642105" target="_blank" >RIV/60077344:_____/25:00642105 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60076658:12310/25:43910323 RIV/61988987:17310/25:A2603CYY

Výsledek na webu

<a href="https://doi.org/10.1093/molbev/msaf289" target="_blank" >https://doi.org/10.1093/molbev/msaf289</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/molbev/msaf289" target="_blank" >10.1093/molbev/msaf289</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The Core MICOS Complex Subunit mic60 has Been Substituted by Two Cryptic Mitofilin-containing Proteins in Euglenozoa

Popis výsledku v původním jazyce

Cristae enclose respiratory chain complexes, making them the bioenergetic subcompartments of mitochondria. The Mitochondrial contact site and Cristae Organizing System (MICOS) complex is among the inducers of membrane curvature needed for crista formation. Resembling the respiratory chain complexes, MICOS is organized around a core protein, the mitofilin-domain bearing Mic60, that was inherited from the alphaproteobacterial progenitor of mitochondria. Extant alphaproteobacteria express Mic60 to form their own bioenergetic subcompartments, demonstrating the permeance of Mic60's form and function during prokaryotic and eukaryotic evolution. Yet, unlike virtually all aerobic eukaryotes, Mic60 is not encoded within the genomes of the multifarious protists that comprise the phylum Euglenozoa, including trypanosomes. Here, we show that Mic60 has been replaced in euglenozoans by two cryptic mitofilin domain-containing MICOS subunits, Mic34 and Mic40. Contrasting alphaproteobacterial and mitochondrial Mic60, these are not integral membrane proteins. Mic34 and Mic40 are as diverged from each other as both are to canonical Mic60. Reverse genetics revealed they are intertwined with the oxidative protein folding pathway required for mitochondrial-and crista-biogenesis, veiling a potential membrane remodeling role. Nevertheless, Mic34 binds phospholipid bilayers in vitro. Mic34 and Mic40 heterologous expression remodels gammaproteobacterial cytoplasmic membranes, like Mic60. Unexpectedly, Mic34 overexpression elaborates the simplified tubular mitochondrion of a Trypanosoma brucei life cycle stage with repressed oxidative phosphorylation. Furthermore, this activity was ablated by mutations to Mic34's mitofilin domain that correspond to essential motifs found in yeast Mic60's mitofilin domain. Thus, the mitofilin protein family is more diverse than originally supposed, with two of its structurally most divergent members altering the core of euglenozoan MICOS.

Název v anglickém jazyce

The Core MICOS Complex Subunit mic60 has Been Substituted by Two Cryptic Mitofilin-containing Proteins in Euglenozoa

Popis výsledku anglicky

Cristae enclose respiratory chain complexes, making them the bioenergetic subcompartments of mitochondria. The Mitochondrial contact site and Cristae Organizing System (MICOS) complex is among the inducers of membrane curvature needed for crista formation. Resembling the respiratory chain complexes, MICOS is organized around a core protein, the mitofilin-domain bearing Mic60, that was inherited from the alphaproteobacterial progenitor of mitochondria. Extant alphaproteobacteria express Mic60 to form their own bioenergetic subcompartments, demonstrating the permeance of Mic60's form and function during prokaryotic and eukaryotic evolution. Yet, unlike virtually all aerobic eukaryotes, Mic60 is not encoded within the genomes of the multifarious protists that comprise the phylum Euglenozoa, including trypanosomes. Here, we show that Mic60 has been replaced in euglenozoans by two cryptic mitofilin domain-containing MICOS subunits, Mic34 and Mic40. Contrasting alphaproteobacterial and mitochondrial Mic60, these are not integral membrane proteins. Mic34 and Mic40 are as diverged from each other as both are to canonical Mic60. Reverse genetics revealed they are intertwined with the oxidative protein folding pathway required for mitochondrial-and crista-biogenesis, veiling a potential membrane remodeling role. Nevertheless, Mic34 binds phospholipid bilayers in vitro. Mic34 and Mic40 heterologous expression remodels gammaproteobacterial cytoplasmic membranes, like Mic60. Unexpectedly, Mic34 overexpression elaborates the simplified tubular mitochondrion of a Trypanosoma brucei life cycle stage with repressed oxidative phosphorylation. Furthermore, this activity was ablated by mutations to Mic34's mitofilin domain that correspond to essential motifs found in yeast Mic60's mitofilin domain. Thus, the mitofilin protein family is more diverse than originally supposed, with two of its structurally most divergent members altering the core of euglenozoan MICOS.

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

Molecular Biology and Evolution

ISSN

0737-4038

e-ISSN

1537-1719

Svazek periodika

42

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

17

Strana od-do

msaf289

Kód UT WoS článku

001618773500001

EID výsledku v databázi Scopus

2-s2.0-105022417053