bims-tricox 2025-08-10 papers

Issue of 2025–08–10
two papers selected by
Yash Verma, University of Zurich

FEBS Lett. 2025 Aug 06.

The cytochrome oxidase defect in ISC-depleted yeast is caused by impaired iron-sulfur cluster maturation of the mitoribosome assembly factor Rsm22.

Ulrich Mühlenhoff, Dominik Trauth, Weronika Śliwińska, Linda Boss, Roland Lill.

Mitochondria contain the bacteria-inherited iron-sulfur cluster assembly (ISC) machinery to generate cellular iron-sulfur (Fe/S) proteins. Mutations in human ISC genes cause severe disorders with a broad clinical spectrum and are associated with strong defects in mitochondrial Fe/S proteins, including respiratory complexes I-III. For unknown reasons, complex IV (aka cytochrome c oxidase), a non-Fe/S, heme-containing enzyme, is severely affected. Using yeast as a model, we show that depletion of Rsm22, the counterpart of the human mitoribosome assembly factor METTL17, phenocopies the defects observed upon impairing late-acting ISC proteins, that is, diminished activities of mitoribosomal translation and respiratory complexes III and IV. Rsm22 binds Fe/S clusters in vivo, thereby satisfactorily explaining the defect of respiratory complex IV in ISC-deficient cells, because this complex contains three mitochondrial DNA-encoded subunits. Impact statement Defects in mitochondrial Fe/S protein biogenesis also impact respiratory complex IV (COX), even though it lacks Fe/S clusters. Here, we show that the mitoribosome assembly factor Rsm22 binds Fe/S clusters in vivo. Rsm22 maturation defects impair mitoribosomal protein translation including COX subunits, explaining the COX defects in Fe/S cluster-deficient cells.

Keywords: biogenesis; cytochromes; iron–sulfur protein; mitochondrial DNA; mitochondrial ribosomes; respiratory chain complexes; translation

DOI: https://doi.org/10.1002/1873-3468.70129

Biol Chem. 2025 Aug 11.

Conserved function, divergent evolution: mitochondrial outer membrane insertases across eukaryotes.

Anna Roza Dimogkioka, Doron Rapaport.

Mitochondrial function relies heavily on the proper targeting and insertion of nuclear-encoded proteins into the outer mitochondrial membrane (OMM), a process mediated by specialised biogenesis factors known as insertases. These insertases are essential for the membrane integration of α-helical OMM proteins, which contain one or multiple hydrophobic transmembrane segments. While the general mechanisms of mitochondrial protein import are well established, recent research has shed light on the diversity and evolutionary conservation of OMM insertases across eukaryotic lineages. In Saccharomyces cerevisiae, the mitochondrial import (MIM) complex, composed of Mim1 and Mim2, facilitates the integration of various α-helical OMM proteins, often in cooperation with import receptors such as Tom20 and Tom70. In Trypanosoma brucei, the functional MIM counterpart pATOM36 performs a similar role despite lacking sequence and structural homology, reflecting a case of convergent evolution. In mammals, MTCH2 has emerged as the principal OMM insertase, with MTCH1 playing a secondary, partially redundant role. This review provides a comparative analysis of these insertases, emphasising their conserved functionality, species-specific adaptations, and mechanistic nuances.

Keywords: MIM complex; MTCH2; insertases; mitochondrial outer membrane; pATOM36

DOI: https://doi.org/10.1515/hsz-2025-0169