bims-mitran 2026-07-05 papers

Issue of 2026–07–05
three papers selected by
Andreas Kohler, Umeå University

Nat Commun. 2026 Jun 30. pii: 5552. [Epub ahead of print]17(1):

Gravitational and mechanical forces shape mitochondrial translation.

Taisei Wakigawa, Yusuke Kimura, Mari Mito, Toshiya Tsubaki, Muhoon Lee, Koki Nakamura, Abdul Haseeb Khan, Hironori Saito, Tohru Yamamori, Tomokazu Yamazaki, Akira Higashibata, Tatsuhisa Tsuboi, Yusuke Hirabayashi, Nono Takeuchi-Tomita, Taku Saito, Atsushi Higashitani, Yuichi Shichino, Shintaro Iwasaki.

Life on Earth has evolved in a form suitable for the gravitational force. Although the pivotal role of gravity in gene expression has been suggested, the molecular details remain unclear. Here, we show that mitochondria utilize gravity to activate protein synthesis within the organelle. Genome-wide ribosome profiling reveals reduced mitochondrial translation in mammalian cells and Caenorhabditis elegans under microgravity. We found that attenuation of cell adhesion through laminin-integrin interactions caused the phenotype. Mitochondrial translation is activated by a signal relayed by FAK, RAC1, PAK1, BAD, and Bcl-2 family proteins in the cytosol, and the mitochondrial fatty acid synthesis (mtFAS) pathway in the matrix. Consumption of mitochondrial malonyl-CoA by mtFAS reduces the malonylation of the translational machinery and accelerates the rates of translational initiation and elongation. Physiologically, this system operates in mechano-response of skeletal muscles. Our work provides mechanistic insights into how cells convert gravitational and mechanical forces into translation in mitochondria.

DOI: https://doi.org/10.1038/s41467-026-74493-z

Bone Res. 2026 Jun 29. pii: 68. [Epub ahead of print]14(1):

Angiogenin mediates cell-cell fusion as a mitochondrial RNA processing enzyme.

Ke Shen, Yixiang Zeng, Jiekang Wang, Kangping Song, Surendra Kumar, Peisong Gao, Guo-Fu Hu, Xu Cao, Mei Wan.

Cell-cell fusion, essential for diverse physiological events, requires high ATP levels. While mitochondrial activity increases in fusing cells, the mechanism driving mitochondrial ribosome (mitoribosome) biogenesis to support these energy demands remains unclear. Here, we identify angiogenin (ANG) as a mitochondrial tRNA (mt-tRNA) processing enzyme critical for mitoribosome biogenesis during myoblast and osteoclast fusion. Upon fusion initiation, ANG translocates to mitochondria, promoting mitoribosome biogenesis to support translation of respiratory complex proteins for ATP production. Using transcriptome-wide PARE and 5' RACE analyses, we show that ANG cleaves the tRNA 3'-end in mitochondrial pre-RNA transcripts bordering rRNAs and mRNAs, enabling their release for translation. Loss of ANG or disruption of its ribonucleolytic activity impairs osteoclast and myoblast fusion, disrupting bone and muscle homeostasis and skeletal muscle regeneration post-injury. Our findings establish ANG as an essential mitoribosome biogenesis regulator and highlight a novel mechanism of mitochondria energy regulation in high-energy-demand biological processes.

DOI: https://doi.org/10.1038/s41413-026-00545-1

Mitochondrion. 2026 Jun 27. pii: S1567-7249(26)00080-2. [Epub ahead of print]91 102190

A neuronal model of mtDNA disease reveals an ineffective reprogramming of the electron transfer chain during neuronal maturation.

Shane Thomas Bell, Rebeca Acín-Pérez, Iffath Ghouri, Jon Meyrick, Robert Lightowlers, Oliver Russell.

Large-scale mitochondrial DNA (mtDNA) deletions can result in deficiency of oxidative phosphorylation and subsequent mitochondrial dysfunction, ultimately leading to mitochondrial disease. To investigate effective treatments, we report a characterised heteroplasmic iPSC-derived neuronal model with a single, large scale ∼6 kb mtDNA deletion. While mtDNA heteroplasmy remains stable during iNGN2-induced neuronal differentiation from iPSCs, the presence of this mtDNA deletion results in an upregulation of mtDNA copy number and compensatory adaptation of oxidative phosphorylation (OXPHOS) machinery. Despite this increase, mitochondrial dysfunction and reduced oxygen consumption is prevalent. Furthermore, as differentiated neurons mature over time, mitochondrial supercomplexes and isolated complex II diminish, suggesting an increase of severity of the mitochondrial dysfunction. In summary, this study provides insight into a novel compensatory mechanism during iPSC differentiation to bypass mitochondrial dysfunction, and how this response exacerbates dysfunction during culture of mature neurons.

Keywords: Complex II; Copy number; Mitochondrial DNA (mtDNA); Mitochondrial dysfunction; Mitochondrial supercomplexes; iPSC-derived neurons

DOI: https://doi.org/10.1016/j.mito.2026.102190