bims-mitran 2026-07-19 papers

Issue of 2026–07–19
two papers selected by
Andreas Kohler, Umeå University

Proc Natl Acad Sci U S A. 2026 Jul 21. 123(29): e2601897123

Dopaminergic neurons preferentially accumulate mtDNA rearrangements.

Tania Arguello, Christian D Alcalde Pretel, Nadee Nissanka, Derek Van Booven, Milena Pinto, Monica Rodriguez-Silva, Lise-Michelle Theard, Anthony J Griswold, Carlos T Moraes.

High levels of mitochondrial DNA (mtDNA) deletions have been described in the substantia nigra. However, the mechanisms involved are poorly understood. We found that transient expression of a mitochondrial targeted restriction endonuclease (mitoPstI) in mice leads to an accumulation of mtDNA rearrangements that involve both the PstI cleavage sites and unrelated specific regions of the mtDNA, including the MTERF1 binding site and the edge of the D-loop. This pattern of rearrangements after double-strand breaks supports the presence of recombination hotspots in the mtDNA. Transient expression of mitoPstI in dopaminergic neurons led to further accumulation of mtDNA rearrangements in dopaminergic neurons after expression was suppressed, a pattern that was not observed in glutamatergic neurons. This accumulation was also blunted when a mtDNA replisome factor was absent, suggesting that robust mtDNA replication is required for the accumulation of preexisting mtDNA rearrangements in dopaminergic neurons over time.

Keywords: Parkinson’s disease; deletions; dopaminergic; double strand break; mtDNA

DOI: https://doi.org/10.1073/pnas.2601897123

Trends Biochem Sci. 2026 Jul 15. pii: S0968-0004(26)00204-5. [Epub ahead of print]

Modification and aminoacylation of human mitochondrial tRNAs.

Shi-Ying Yao, Meng Wang, Fan-Yan Wei, Xiao-Long Zhou.

Mitochondrial tRNAs (mt-tRNAs) are central to energy production by translating essential oxidative phosphorylation subunits. Following transcription, mt-tRNAs undergo diverse processing steps, post-transcriptional modifications, and aminoacylation, which are critical for their functions. In this article, we review how human mt-tRNA-modifying enzymes deposit various post-transcriptional modifications onto mt-tRNAs, encompassing both well-characterized and less-understood marks. We also summarize the principles, peculiarities, and critical roles of mt-tRNA charging and proofreading, and highlight recently uncovered noncanonical functions of mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs). Collectively, these recent findings demonstrate the dynamic regulatory mechanisms of mt-tRNA modification and aminoacylation, the extensive involvement of mt-aaRSs in cellular metabolic pathways, and the promising potential of targeting these enzymes in therapeutics.

Keywords: editing; mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs); mitochondrial diseases; mitochondrial translation; noncanonical functions; post-transcriptional modification

DOI: https://doi.org/10.1016/j.tibs.2026.06.009