bims-mitran 2026-06-07 papers

Issue of 2026–06–07
two papers selected by
Andreas Kohler, Umeå University

J Biol Chem. 2026 Jun 04. pii: S0021-9258(26)02107-1. [Epub ahead of print] 113235

Ago1 is required for the regulation of mitochondrial translation under heat stress in S. pombe.

Mengling Yu, Yuanqi Xu, Yijing Lu, Minjie Li, Yucheng Yao, Gang Feng, Ying Huang, Jinjie Shang.

Mitochondrial protein synthesis is a critical component of OXPHOS complexes, vital for both mammals and Schizosaccharomyces pombe. In our study, we investigated the effect of heat stress on mitochondria, analyzed the mitochondrial proteome and found that during heat stress, the translation of all mtDNA-encoded transcripts was impaired, leading to a reduction in the steady-state levels of mtDNA-encoded proteins, suggesting that heat stress plays a general role in mitochondrial protein synthesis. We also found that heat stress affects the association of mitochondrial translation initiation factors to mitoribosomal small subunits. Interestingly, ago1 deletion compensates for the heat-induced disruption of the interaction between mitochondrial translation initiation factor and mitoribosomes, leading to partial recovery of both translation and steady-state levels of mtDNA-encoded proteins in S. pombe. Under heat stress, Ago1 accumulates in the mitochondrial matrix. C-terminal truncation ablates this localization and abolishes rescue of translational suppression, confirming mitochondrial targeting is essential for regulatory function. Furthermore, our data demonstrate that Ago1's small RNA-loading related N-terminal domain is required for heat-induced translational suppression and that Ago1 physically engages with mitochondrial RNAs, collectively indicating potential RNA interference (RNAi) activity within mitochondria. These findings provide insight into the regulation of mitochondrial protein synthesis in heat stress.

Keywords: Heat stress; Mitochondria; Mitochondrial protein synthesis; Mitochondrial translation; Schizosaccharomyces pombe

DOI: https://doi.org/10.1016/j.jbc.2026.113235

Hum Mol Genet. 2026 Jun 01. pii: ddag042. [Epub ahead of print]35(10):

MRPS22 variants alter mitochondrial ribosome assembly in patients with leukodystrophy, movement disorder and intellectual impairment.

Ruth I C Glasgow, Finn Lennartsson, Snjolaug Arnardottir, Dmitrii Igorevich Shiriaev, Sandrina P Correia, Marco Moedas, Lucía Peña-Pérez, Martin Paucar, Karin Naess, Helene Bruhn, Nicole Lesko, Rolf Wibom, Joanna Rorbach, Christoph Freyer, Anna Wedell, Sofia Ygberg, Erik A Eklund, Anna Wredenberg.

Mitochondrial diseases are clinically and genetically heterogeneous, often complicating diagnosis. Here, we describe four unrelated individuals with suspected mitochondrial disease who shared similar neuroimaging features, including bilateral symmetrical supra- and infratentorial white-matter abnormalities, together with variable movement disorders and intellectual impairment. Whole-genome sequencing identified the same homozygous MRPS22 variant (c.798_799delinsTA) in all four patients. MRPS22 encodes a component of the mitochondrial small ribosomal subunit (mtSSU). Functional studies in patient-derived fibroblasts showed impaired mitoribosome assembly and reduced de novo mitochondrial translation. Despite largely preserved steady-state levels of OXPHOS proteins, respiratory chain analysis identified a mild, isolated complex I deficiency. Proteomic profiling revealed reduced levels of mitochondrial ribosomal proteins and dysregulation of mitochondrial translation pathways. In line with the proteomic findings, RNA sequencing of fibroblasts from three patients revealed a distinct transcriptional signature compared with controls, with mitochondrial translation emerging as the most affected pathway. Mitochondrial-encoded transcripts were decreased, whereas nuclear-encoded mitochondrial genes were generally increased. Structural modelling suggested that the variant disrupts key interactions important for mitoribosome stability. While previously reported MRPS22 variants have been associated with severe, often prenatal-onset disease, the individuals described here exhibited a milder phenotype, thereby expanding the clinical spectrum of MRPS22-related disorders. Together, these findings support the pathogenicity of this variant and highlight the value of integrated genomic and functional analyses in diagnosing mitochondrial disease.

Keywords: MRPS22; adult-onset; mS22; mitochondrial ribosome; translation

DOI: https://doi.org/10.1093/hmg/ddag042