bims-mitran 2026-02-15 papers

Issue of 2026–02–15
three papers selected by
Andreas Kohler, Umeå University

Nat Rev Mol Cell Biol. 2026 Feb 13.

Mechanisms and disease relevance of mitochondrial translation in humans.

Ricarda Richter-Dennerlein, Xaquin Castro Dopico, Joanna Rorbach.

Human mitochondrial ribosomes (mitoribosomes) synthesize the 13 mitochondrial-encoded proteins of the oxidative phosphorylation machinery in a coordinated manner, ensuring proper folding of nascent peptides into the inner mitochondrial membrane and their dynamic assembly with nuclear-encoded oxidative phosphorylation components. Our understanding of mitochondrial translation is rapidly advancing, and in this Review, we discuss recent studies that reveal the intricate regulation of mitochondrial translation initiation, elongation and termination, ribosome biogenesis, redox sensing, mitochondrial mRNA maturation, and quality control mechanisms such as mitoribosome rescue. High-resolution structural studies, mitoribosome profiling and other innovative methodologies provide comprehensive insights into these regulatory networks. We also discuss pathological consequences of mitochondrial translation dysfunction, particularly antibiotic-induced ribosome stalling, which can have severe side effects in some individuals and therapeutic benefits in others. Relatedly, we discuss the emerging roles and clinical relevance of mitochondrial protein synthesis in cancer and immunity. Finally, we outline future directions in the field, including in vitro reconstitution of mitochondrial translation, gene editing in mitochondrial DNA and therapeutic applications.

DOI: https://doi.org/10.1038/s41580-026-00948-2

Nat Commun. 2026 Feb 09.

Structural basis of TACO1-mediated efficient mitochondrial translation.

Shuhui Wang, Michele Brischigliaro, Yuekang Zhang, Chunxiang Wu, Wei Zheng, Antoni Barrientos, Yong Xiong.

Translation elongation is a universally conserved step in protein synthesis, relying on elongation factors that engage the ribosomal L7/L12 stalk to mediate aminoacyl-tRNA delivery, accommodation, and ribosomal translocation. Using in organello cryo-electron microscopy, we reveal how the mitochondrial translation accelerator TACO1 promotes efficient elongation on human mitoribosomes. TACO1 binds the mitoribosomal region typically bound by elongation factor Tu (mtEF-Tu), bridging the large and small subunits via contacts with 16S rRNA, bL12m, A-site tRNA, and uS12m. While active throughout elongation, TACO1 is especially critical when translating polyproline motifs. Its absence prolongs mtEF-Tu residence in A/T states, causes persistent mitoribosomal stalling and premature subunit dissociation. Structural analyses indicate that TACO1 competes with mtEF-Tu for mitoribosome binding, stabilizes A-site tRNA, and enhances peptidyl transfer through a mechanism distinct from EF-P and eIF5A. These findings suggest that bacterial TACO1 orthologs may serve analogous roles, highlighting an evolutionarily conserved strategy for maintaining elongation efficiency during challenging translation events.

DOI: https://doi.org/10.1038/s41467-026-69156-y

Adv Sci (Weinh). 2026 Feb 12. e23462

Illuminating Mitochondrial RNA G-Quadruplexes as Structural Brakes on RNA Granule Assembly and OXPHOS.

Gui-Xue Tang, Jia-Tong Yan, Mao-Lin Li, Cui Zhou, Jian Wang, Shuo-Bin Chen, Zhi-Shu Huang, Jia-Heng Tan.

G-quadruplexes (G4s) have been extensively investigated in cells, with established methods available for studying nuclear DNA G4s, cytoplasmic RNA G4s, and even mitochondrial DNA G4s. However, mitochondrial RNA (mtRNA) G4s have remained largely unexplored in cells due to the lack of suitable tools, leaving their biological functions poorly understood. Here, through rational molecular design, we developed MitoQUMA, a fluorescent probe that allows the visualization of mtRNA G4 dynamics in live cells. Using this probe, we observed that, unlike cytoplasmic RNA G4s, which generally promote phase separation to form RNA granules, excessive formation of mtRNA G4s correlates with reduced assembly of mitochondrial RNA granules (MRGs). A MitoQUMA-based chemical genetic screen revealed that the Wnt/β-catenin pathway regulates this mitochondrial event by modulating GRSF1 expression, thereby affecting mtRNA G4 abundance and processing. When RNA processing is compromised, mtRNA maturation is impaired, and MRG becomes unstable and undergoes disassembly, ultimately disrupting mitochondrial gene expression and energy metabolism. Collectively, our study introduces a tool for real-time monitoring of mtRNA G4s in cells and identifies the Wnt/β-catenin-GRSF1-mtRNA G4 axis as a previously unrecognized pathway coordinating MRG assembly and energy metabolism, providing new insights into phase separation within mitochondria.

Keywords: GRSF1; Wnt/β‐catenin pathway; mitochondrial RNA G‐quadruplex; mitochondrial RNA granule; molecular probe

DOI: https://doi.org/10.1002/advs.202523462