bims-mitran 2026-02-01 papers

Issue of 2026–02–01
three papers selected by
Andreas Kohler, Umeå University

World J Clin Oncol. 2026 Jan 24. 17(1): 113600

Pleiotropic regulation of mitochondrial translational factors in governing proliferation, apoptosis and metastasis during cancer progression.

Nikita Agarwal, Uttam Sharma, Akshi Shree, Rajiv Ranjan Kumar, Jaya Kanta Gorain, Vaishnavi Vishwas, Farhana Jahan, Archna Singh, Jayanth Kumar Palanichamy, Deepam Pushpam, Radhika Bakhshi, Anita Chopra, Ranjit Kumar Sahoo, Atul Batra, Surender K Sharawat, Sameer Bakhshi.

Mitochondrial translation relies on the coordinated activity of mitoribosomes, mitochondrial ribosome proteins, mitochondria-specific transfer RNAs, and dedicated translation factors, including mitochondrial initiation factor 2/3, mitochondrial elongation factor Tu, mitochondrial elongation factor Ts, mitochondrial elongation factor G1/G2, mitochondrial elongation factor 4, mitochondrial ribosome recycling factor, and mitochondrial release factor 1A. These components collectively drive the synthesis of 13 essential polypeptides encoded by mitochondrial DNA, all constituting subunits of the oxidative phosphorylation complexes. Although mitochondrial metabolism is increasingly recognized as a key player in cancer, the specific contribution of mitochondrial translation to cancer progression remains poorly explored. This gap in knowledge limits our understanding of how mitochondrial dysfunction contributes to tumor initiation, progression, and therapy resistance. Herein, in this review, we highlight how dysregulation of mitochondrial translation factors can influence major cancer hallmarks such as sustained proliferative signaling, resistance to apoptosis, and increased invasion and metastasis. In addition, we discuss the known molecular mechanisms that link defects in mitochondrial translation to oncogenic features. We also consolidate current insights into the mitochondrial translation machinery and discuss recent evidence of its role in cancer, aiming to emphasize mitochondrial translation as a contributor to malignancy and a potential therapeutic target.

Keywords: Cancer; Hallmark; Mitochondrial ribosomal proteins; Mitochondrial translation; Mitochondrial translation factors

DOI: https://doi.org/10.5306/wjco.v17.i1.113600

Cells. 2026 Jan 10. pii: 127. [Epub ahead of print]15(2):

Targeting of Human Mitochondrial DNA with Programmable pAgo Nuclease.

Beatrisa Rimskaya, Ekaterina Kropocheva, Elza Shchukina, Egor Ulashchik, Daria Gelfenbein, Lidiya Lisitskaya, Vadim Shmanai, Svetlana Smirnikhina, Andrey Kulbachinskiy, Ilya Mazunin.

Manipulating the mitochondrial genome remains a significant challenge in genetic engineering, primarily due to the mitochondrial double-membrane structure. While recent advances have expanded the genetic toolkit for nuclear and cytoplasmic targets, precise editing of mitochondrial DNA (mtDNA) has remained elusive. Here we report the first successful mitochondrial import of a catalytically active RNA-guided prokaryotic Argonaute protein from the mesophilic bacterium Alteromonas macleodii (AmAgo). By guiding AmAgo to the single-stranded D- or R-loop region of mtDNA using synthetic RNA guides, we observed a nearly threefold reduction in mtDNA copy number in human cell lines. This proof of concept study demonstrates that a bacterial Argonaute can remain active within the mitochondrial environment and influence mtDNA levels. These findings establish a foundational framework for further development of programmable systems for mitochondrial genome manipulation.

Keywords: DNA editing; mitochondria; mtDNA copy number; prokaryotic Argonaute proteins

DOI: https://doi.org/10.3390/cells15020127

Nat Commun. 2026 Jan 29.

ALKB-1-dependent tRNA methylation is required for efficient paternal mitochondrial elimination.

Zhenhuan Luo, Yimin Li, Chenyang He, Dan Wu, Wenyu Dai, Liubing Hu, Jing Yang, Brian L Harry, Zhenyu Ju, Nektarios Tavernarakis, Hao Wang, Qin-Li Wan, Qinghua Zhou.

Maternal mitochondrial inheritance is secured by mechanisms that exclude paternal mitochondrial DNA (mtDNA). While, epigenetic modifications are vital for spermatogenesis and embryo development, their roles in the paternal mitochondrial elimination (PME) remain poorly understood. Here, we identify ALKB-1, a DNA/RNA demethylase, as a pivotal factor for efficient PME in Caenorhabditis elegans (C. elegans), acting through ALKB-1-dependent modulation of tRNA m1A methylation. Mechanistically, ALKB-1 inactivation leads to m1A hypermethylation of tRNA, which subsequently disrupts protein translation, impairs mitochondrial proteostasis, and increases ROS levels. This cascade activates the oxidative stress response factor SKN-1/Nrf2 and initiates the mitochondrial unfolded protein response (UPRmt) through ATFS-1, causing accumulation of mitochondria and mtDNA in sperm, which ultimately impedes efficient paternal mitochondrial removal and negatively impacts male fertility and embryonic development. Our findings describe a mechanism whereby ALKB-1-mediated tRNA m1A epitranscriptomic modifications are necessary for maintaining mitochondrial quality control, thereby influencing PME efficiency, underscoring the importance of this epitranscriptomic stress checkpoint in upholding proper mitochondrial inheritance during reproduction.

DOI: https://doi.org/10.1038/s41467-026-68813-6