bims-mitran 2026-03-01 papers

Issue of 2026–03–01
two papers selected by
Andreas Kohler, Umeå University

Sci Adv. 2026 Feb 27. 12(9): eaeb0049

Specific SLC25 carriers regulate mitochondrial protein synthesis.

Danielle L Rudler, Laetitia A Hughes, Martin S King, Jessica Baker, Richard G Lee, Andrianto P Gandadireja, Anisha Sunil, Samuel V Fagan, Blake Payne, Nicola Gray, Tim McCubbin, Edmund R S Kunji, Oliver Rackham, Aleksandra Filipovska.

A genome-wide knockout screen identified members of the SLC25 family of mitochondrial carrier proteins as important regulators of the rate of de novo mitochondrial protein synthesis. To elucidate this relationship, we generated human cell knockouts for SLC25A25, SLC25A44, SLC25A45, and SLC25A48, which have been shown to exchange adenosine triphosphate-magnesium (ATP-Mg) and phosphate, branched-chain amino acids, methylated basic amino acids, and choline, respectively. Multiomic and functional analyses identified that these four carriers are crucial for mitochondrial translation, biogenesis and function of the oxidative phosphorylation system, as well as mitochondrial morphology. Thermostability screens showed that SLC25A48 is specifically stabilized by choline, and changes in the mitochondrial metabolome and lipidome indicated defects in choline biosynthetic pathways and remodeling of mitochondrial membranes, both consistent with SLC25A48 being a choline transporter. These results highlight the essential roles of specific SLC25 transporters in maintaining mitochondrial structure and function and show that impaired transport of branched-chain amino acids, methylated basic amino acids, ATP-Mg, and choline affects mitochondrial translation.

DOI: https://doi.org/10.1126/sciadv.aeb0049

Nat Commun. 2026 Feb 23.

PRMT5 in mitochondria regulates mtDNA stability through TFAM arginine methylation.

Sangheeta Bhattacharjee, Sayan Das, Banhi Chowdhury, Benu Brata Das.

Protein arginine methyltransferase 5 (PRMT5) catalyzes arginine methylation and regulates cellular functions such as proliferation, RNA splicing, and nuclear DNA damage response. This study uncovers that a fraction of nuclear-encoded PRMT5 localizes to the mitochondria, which is critical for maintaining mitochondrial DNA (mtDNA) homeostasis. PRMT5 knockout (PRMT5-/-) cells had reduced nucleoid counts, diminished mtDNA copy numbers, disrupted the balance of the mitochondrial fission-fusion cycle, impaired mitochondrial plasticity, and nucleoid trafficking. PRMT5-/- cells are hypersensitive to mtDNA-damaging agents, exhibit reduced mitochondrial transcripts, oxidative phosphorylation, and respiratory capacity that triggers cell death. We identify TFAM as a previously unrecognized interacting partner of PRMT5, which catalyzes symmetric dimethylation of TFAM at R82 residue, which is crucial for mtDNA binding and protection. Defective R82-methylation destabilizes TFAM, which is then degraded by LonP1. Together, we establish that PRMT5 is a mitochondrial enzyme and a key regulator of TFAM in mtDNA maintenance.

DOI: https://doi.org/10.1038/s41467-026-69676-7