bims-tricox 2026-06-28 papers

Issue of 2026–06–28
three papers selected by
Yash Verma, Universität Zürich

Nat Commun. 2026 Jun 24. pii: 5564. [Epub ahead of print]17(1):

Pseudouridine synthase PUS1 and initiation factor mtIF2 are human mitoribosomal small subunit assembly factors.

Vivek Singh, Dmitrii Shiriaev, Lorina Bilalli, Anas Khawaja, Joanna Rorbach.

Assembly of the mitochondrial ribosome (mitoribosome) is a crucial step in mitochondrial gene expression. This process facilitates mitochondrial translation, which produces essential subunits of the oxidative phosphorylation machinery-the cell's primary energy-producing machinery. Disruptions in mitoribosome assembly can lead to severe human diseases. Given its fundamental importance, detailed structural analysis of mitoribosome assembly pathways is essential for advancing our understanding of mitochondrial function in both health and disease. In this study, we characterize twelve distinct assembly states of the mitoribosomal small subunit (mtSSU) isolated from human cells. Our findings reveal the intricate details of the final maturation stages of the mtSSU platform, decoding center, and the 3'-end of 12S rRNA. This process is governed by coordinated actions of assembly factors that ensure precise, stepwise rRNA folding and the integration of mitoribosomal proteins into the developing subunit. Our approach identifies pseudouridine synthase PUS1 and initiation factor mtIF2 as assembly factors, expanding their known roles beyond mt-tRNA maturation and translation, respectively. In addition, the identified assembly intermediates provide insight into the modular nature of mtSSU biogenesis in mitochondria and further link late-stage assembly to the acquisition of translational competence.

DOI: https://doi.org/10.1038/s41467-026-74700-x

Adv Exp Med Biol. 2026 ;1514 85-111

The TOM Complex in the Outer Membrane of Mitochondria: A Supramolecular Assembly for Protein Import.

Stephan Nussberger, Robin Ghosh, Shuo Wang.

Currently, there is no comprehensive physical model explaining how unfolded polypeptide chains with diverse characteristics are transported into the mitochondria. On a molecular scale, the kinetics of how transit polypeptides approach, are captured by the protein translocation machinery at the outer mitochondrial membrane, and cross the protein translocation pore to enter the intermembrane space remain unclear. This knowledge gap is primarily due to the lack of dynamic single-molecule data on the "protein-conducting channels" involved in mitochondrial protein translocation. In this chapter, we explore the recently resolved sub-nanometer cryo-EM structures, which are a prerequisite for a fundamental understanding of the translocation mechanism, and our existing knowledge of the mitochondrial two-pore outer membrane protein translocation machinery (TOM complex). Particularly intriguing are recent findings from single-molecule TIRF microscopy indicating that the TOM core complex can function as a mechanosensor, with the pores closing upon interaction with nearby membrane structures. We emphasize novel and unexpected correlations between the structural components of the TOM complexes and their dynamic behavior within the membrane environment.

Keywords: Droplet interface bilayer membranes; Electron cryo-microscopy; Mechanosensitivity; Mitochondria; Native mass spectrometry; Protein import; Single-molecule fluorescence microscopy; TOM complex

DOI: https://doi.org/10.1007/978-3-032-26629-3_5

Biochem J. 2026 Jul 08. 483(7): 1253-1280

Proteolytic coordination of the OXPHOS Life Cycle.

Nataliia Nechytailo, Karolina Szczepanowska.

The mitochondrial oxidative phosphorylation (OXPHOS) system consists of multimeric, highly ordered protein complexes critical for energy production and metabolic wiring in the cell. Recent discoveries in mitochondrial proteolysis, facilitated by advances in proteomic approaches, have transformed the view of mitochondrial proteases from a simple quality-control system into a dynamically coordinated network of enzymes that actively shape the status of the OXPHOS machinery. Mapping OXPHOS-associated proteolytic circuits has uncovered specialized functions of individual proteases and identified key interaction sites. The present review outlines how mitochondrial proteases regulate the OXPHOS life cycle: expression, delivery, assembly, long-term maintenance, and disposal of mitochondrial respiratory complexes. We summarize past findings and highlight emerging concepts, including asynchronous OXPHOS turnover, cofactor-driven proteolysis, and bioenergetics-coupled degradation. Progress in these areas will deepen our understanding of how proteases coordinate the OXPHOS life cycle.

Keywords: mitochondria; mitochondrial proteases; mitochondrial respiratory complexes; oxidative phosphorylation; regulatory proteolysis; turnover

DOI: https://doi.org/10.1042/BCJ20250120