Next Article in Journal
MHC Class II and Beyond: Complex Role of CD74 in Cancer
Next Article in Special Issue
Cyclophilin D, Regulator of Mitochondrial Permeability Transition and Bioenergetics, Promotes Adipogenic Differentiation of Mesenchymal Stem Cells
Previous Article in Journal
Cancer Immunomodulatory Effect of Bidens pilosa L. in Mice: Suppression of Tumor-Associated Macrophages and Regulatory T Cells
Previous Article in Special Issue
Dissecting the Biological Functions of Various Isoforms of Ferredoxin Reductase for Cell Survival and DNA Damage Response
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Cells
Volume 15
Issue 2
10.3390/cells15020127
cells-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Targeting of Human Mitochondrial DNA with Programmable pAgo Nuclease

by
Beatrisa Rimskaya
1,2,
Ekaterina Kropocheva
2,3,
Elza Shchukina
1,
Egor Ulashchik
4,
Daria Gelfenbein
3,
Lidiya Lisitskaya
3,
Vadim Shmanai
4,
Svetlana Smirnikhina
5,
Andrey Kulbachinskiy
3 and
Ilya Mazunin
2,6,*
1
Moscow Center for Advanced Studies, 123592 Moscow, Russia
2
The Center for Bio- and Medical Technologies, 121205 Moscow, Russia
3
Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia
4
Institute of Physical Organic Chemistry, National Academy of Science of Belarus, 220072 Minsk, Belarus
5
Research Centre for Medical Genetics, 115478 Moscow, Russia
6
Department of Biology and Genetics, Petrovsky Medical University, 119435 Moscow, Russia
*
Author to whom correspondence should be addressed.
Cells 2026, 15(2), 127; https://doi.org/10.3390/cells15020127
Submission received: 4 December 2025 / Revised: 8 January 2026 / Accepted: 9 January 2026 / Published: 10 January 2026
(This article belongs to the Special Issue Mitochondria at the Crossroad of Health and Disease—Second Edition)
Browse Figures
Versions Notes

Abstract

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: mitochondria; DNA editing; prokaryotic Argonaute proteins; mtDNA copy number mitochondria; DNA editing; prokaryotic Argonaute proteins; mtDNA copy number
Graphical Abstract

Share and Cite

MDPI and ACS Style

Rimskaya, B.; Kropocheva, E.; Shchukina, E.; Ulashchik, E.; Gelfenbein, D.; Lisitskaya, L.; Shmanai, V.; Smirnikhina, S.; Kulbachinskiy, A.; Mazunin, I. Targeting of Human Mitochondrial DNA with Programmable pAgo Nuclease. Cells 2026, 15, 127. https://doi.org/10.3390/cells15020127

AMA Style

Rimskaya B, Kropocheva E, Shchukina E, Ulashchik E, Gelfenbein D, Lisitskaya L, Shmanai V, Smirnikhina S, Kulbachinskiy A, Mazunin I. Targeting of Human Mitochondrial DNA with Programmable pAgo Nuclease. Cells. 2026; 15(2):127. https://doi.org/10.3390/cells15020127

Chicago/Turabian Style

Rimskaya, Beatrisa, Ekaterina Kropocheva, Elza Shchukina, Egor Ulashchik, Daria Gelfenbein, Lidiya Lisitskaya, Vadim Shmanai, Svetlana Smirnikhina, Andrey Kulbachinskiy, and Ilya Mazunin. 2026. "Targeting of Human Mitochondrial DNA with Programmable pAgo Nuclease" Cells 15, no. 2: 127. https://doi.org/10.3390/cells15020127

APA Style

Rimskaya, B., Kropocheva, E., Shchukina, E., Ulashchik, E., Gelfenbein, D., Lisitskaya, L., Shmanai, V., Smirnikhina, S., Kulbachinskiy, A., & Mazunin, I. (2026). Targeting of Human Mitochondrial DNA with Programmable pAgo Nuclease. Cells, 15(2), 127. https://doi.org/10.3390/cells15020127

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop