Mutant mitochondrial helicase Twinkle causes multiple mtDNA deletions and a late-onset mitochondrial disease in mice

Premature ageing in mice expressing defective mitochondrial DNA polymerase

Trifunovic, A., Wredenberg, A., Falkenberg, M., Spelbrink, J. N., Rovio, A. T., Bruder, C. E., Bohlooly-Y, M., Gidlöf, S., Oldfors, A., Wibom, R., et al. (2004) · Nature · doi:10.1038/nature02517 · Cited by 2,734

Human mitochondrial DNA deletions associated with mutations in the gene encoding twinkle, a phage T7 gene 4-like protein localized in mitochondria

Spelbrink, J. N., Li, F.-Y., Tiranti, V., Nikali, K., Yuan, Q.-P., Tariq, M., Wanrooij, S., Garrido, N., Comi, G., Morandi, L., et al. (2001) · Nature Genetics · doi:10.1038/90058 · Cited by 882

Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions

Van Goethem, G., Dermaut, B., Löfgren, A., Martin, J.-J., & Van Broeckhoven, C. (2001) · Nature Genetics · doi:10.1038/90034 · Cited by 841

An autosomal dominant disorder with multiple deletions of mitochondrial DNA starting at the D-loop region

Zeviani, M., Servidei, S., Gellera, C., Bertini, E., DiMauro, S., & DiDonato, S. (1989) · Nature · doi:10.1038/339309a0 · Cited by 636

mtDNA depletion with variable tissue expression: a novel genetic abnormality in mitochondrial diseases.

Moraes, C. T., Shanske, S., Tritschler, H., Aprille, J. R., Andreetta, F., Bonilla, E., Schon, E. A., & DiMauro, S. (1991) · PubMed · Cited by 586

A mouse model for mitochondrial myopathy and cardiomyopathy resulting from a deficiency in the heart/muscle isoform of the adenine nucleotide translocator

Graham, B. H., Waymire, K. G., Cottrell, B. A., Trounce, I. A., MacGregor, G. R., & Wallace, D. C. (1997) · Nature Genetics · doi:10.1038/ng0797-226 · Cited by 556

Parkinsonism, premature menopause, and mitochondrial DNA polymerase γ mutations: clinical and molecular genetic study

Luoma, P., Melberg, A., Rinne, J. O., Kaukonen, J. A., Nupponen, N. N., Chalmers, R. M., Oldfors, A., Rautakorpi, I., Peltonen, L., Majamaa, K., et al. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16983-3 · Cited by 548

Crystal Structure of T7 Gene 4 Ring Helicase Indicates a Mechanism for Sequential Hydrolysis of Nucleotides

Singleton, M. R., Sawaya, M. R., Ellenberger, T., & Wigley, D. B. (2000) · Cell · doi:10.1016/s0092-8674(00)80871-5 · Cited by 472

POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion

Naviaux, R. K., & Nguyen, K. V. (2004) · Annals of Neurology · doi:10.1002/ana.20079 · Cited by 459

Reconstitution of a minimal mtDNA replisome in vitro

Korhonen, J. A., Pham, X. H., Pellegrini, M., & Falkenberg, M. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600257 · Cited by 404

Mammalian Resilience Revealed by a Comparison of Human Diseases and Mouse Models Associated With DNA Helicase Deficiencies

Kohzaki, M. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.934042 · Cited by 1

Molecular mechanisms of aging in MTDNA mutator mice

Edgar, D. (2011) · Figshare · Cited by 1

Twinkle is not the mitochondrial DNA replicative helicase in C. elegans , but may have alternate mitochondrial functionsPreprint

Henderson, H. R., Euro, L., Suomalainen, A., & Dillin, A. G. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/497305 · Cited by 1

De novo serine biosynthesis is protective in mitochondrial diseasePreprint

Jackson, C. B., Marmyleva, A., Awadhpersad, R., Monteuuis, G., Mito, T., Zamboni, N., Tatsuta, T., Vincent, A. E., Wang, L., Langer, T., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.03.23.533952 · Cited by 1

Lysosomal uptake of mtDNA mitigates heteroplasmyPreprint

Kakanj, P., Bonse, M., Gökmen, A., Gaedke, F., Mollá, B., Vogelsang, E., Schauss, A. C., Wodarz, A., & Pla‐Martín, D. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.02.16.580263 · Cited by 1

Mitochondrial Involvement in Neurodegeneration and Aging

Pickrell, A. M. (2012)

The effects of mitochondrial DNA mutagenesis on somatic stem cells and ageing

Ahlqvist, K. J. (2015) · Työväentutkimus Vuosikirja

The impact of mitochondria on preimplantation development in the rhesus macaque

Gibson, T. C. (2010) · Human Biology

Molecular insights into mitochondrial dna replication

Fusté, J. M. (2012) · Figshare

MECHANISMS AND EFFECTS OF MITOCHONDRIAL DNA INSTABILITY AND COPY NUMBER MANIPULATION

Ylikallio, E. (2011) · Työväentutkimus Vuosikirja

Current Progress and Future Perspectives: Toward Mitochondrial Medicine

Marı́n-Garcı́a, J. (2012) · Springer eBooks · doi:10.1007/978-1-4614-4599-9_24

Mitochondrial dysfunction and treatment strategies

Krishnan, S. (2016) · Figshare

Clinical and genotypic aspects of mitochondrial disease

Gorman, G. S. (2015)

Neuropathological characterization of FL-PGC-1α-deficient mice – implications for mitochondrial encephalopathy

Szalárdy, L. (2016) · SZTE Repository of Dissertations (University of Szeged) · doi:10.14232/phd.3120 · Cited by 1

Manifestations of Drug Toxicity on Mitochondria in the Nervous System

Prehn, J. H. M., & Llorente‐Folch, I. (2018) · Wiley eBooks · doi:10.1002/9781119329725.ch9

Helicases and Their Relevance to Aging

Crouch, J. D., Banerjee, T., Awate, S., Bharti, S. K., & Brosh, R. M. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811353-0.00072-5

Model Cells and Organisms in Mitochondrial Diseases

Stefanatos, R. K. A., Sanz, A., & Fernández‐Ayala, D. J. M. (2021) · Springer eBooks · doi:10.1007/978-3-030-70147-5_10

Faculty Opinions recommendation of Ant1 mutant mice bridge the mitochondrial and serotonergic dysfunctions in bipolar disorder.

Nakajima, T., & Fujita, H. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.733430766.793547337

Papers of Note

(2005) · Science of Aging Knowledge Environment · doi:10.1126/sageke.2005.47.nw44

Adenine base editing corrects point mutation in mitochondrial single-stranded binding protein ( SSBP1 ) to improve mitochondrial functionPreprint

Cha, J. H., Lee, S., Yun, Y., Choi, W. H., Koo, H., Jung, S. H., Chae, H. B., Lee, D. H., Lee, S. J., Jo, D. H., et al. (2023) · medRxiv · doi:10.1101/2023.11.02.23297943

Skeletal Muscle Specific PolG Dysfunction Activates the Integrated Stress Response and Promotes a Cachexia like PhenotypePreprint

Bond, S. T., King, E. J., Walker, S., Yang, C., Liu, Y., Liu, K. H., Zhuang, A., Jurrjens, A. W., Fang, H., Formosa, L. E., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.02.597064

Coenzyme I and Skeletal Muscle Disorders

Jiang, Z., Luo, L., Qin, Y., Zhou, Y., & Zhao, F. (2025) · Springer eBooks · doi:10.1007/978-981-97-9877-3_30

Modelling mitochondrial diseases in neurons In Vitro : A systematic review

Zarate-Mendez, M., Basha, N., Podmanicky, O., Malig, N., Hathazi, D., & Horváth, R. (2025) · Journal of Neuromuscular Diseases · doi:10.1177/22143602241307198

Recessive variants in TWNK cause syndromic and non-syndromic post-synaptic auditory neuropathy through MtDNA replication defects

Gao, X., Ma, Y., Wang, W., Wang, G., Yang, K., Xu, J., Huang, S.-S., Wang, X., Hu, L.-M., Wang, X., et al. (2025) · Human Genetics · doi:10.1007/s00439-025-02774-6

Patient-derived TWNK variants recapitulate multisystem Perrault syndrome pathology in a mouse model

Wang, W., Dong, X., Cao, C., Li, H.-B., & Lv, Y.-F. (2026) · Mitochondrion · doi:10.1016/j.mito.2026.102137

Ring Shift

Gakely, G. (2026) · Annals of Rejuvenation Science · doi:10.65649/rm9epe20

Mitochondrial DNA Deletions in Peripheral Blood of the Offspring of Workers Exposed to Occupational Chronic Ionizing Irradiation

Lomaeva, M. G., Zakharova, M. L., Azizova, T. V., & Antipova, V. N. (2025) · BIOPHYSICS · doi:10.1134/s0006350925700927

Déficits de la chaîne respiratoire mitochondriale avec instabilité de l’ADN mitochondrial : identification de nouveaux gènes et mécanismes

Berg-Alonso, L. (2016) · theses.fr (ABES) · doi:10.70675/4e84cd52z03a4z4a6cz95d5z5c7dbdfc7708

Utilisation du modèle levure pour la recherche de voies thérapeutiques contre le syndrome de Barth

de Tilques, M. D. T. (2017) · theses.fr (ABES) · doi:10.70675/db54cf9cz39cdz47d7z9aabz808ab0c7b1c7

Onward and Downward: Aging Theories, Philosophies, and Fallacies

Cramer, J. G. (2026) · Copernicus books · doi:10.1007/978-3-032-17741-4_3

Loss of mitochondrial DNA helicase in retinal macroglia drives neovascular retinopathy

Olander, S., Karaman, S., Suomi, F., Aguilar, K., Zhaivoron, A., Nedergaard, M., Smeds, L., Tiihonen, J., Quintana, A., Hidalgo, J., et al. (2026) · EMBO Molecular Medicine · doi:10.1038/s44321-026-00438-0

Loss of mitochondrial co-chaperone GRPEL2 protects mice from age- and diet-induced obesity

Yang, Y., Neupane, N., Kvist, J., Saarimäki‐Vire, J., Schewe, M., Luopajärvi, K., Manjunath, P., Konovalova, S., Torregrosa‐Muñumer, R., Kinnunen, V., et al. (2026) · Mitochondrion · doi:10.1016/j.mito.2026.102205

Systematic Profiling and Functional Characterization of Alternative Splicing in C. elegans Olfactory LearningPreprint

Chen, M., Wu, M., Koterniak, B., Ge, M., Liang, J., Calarco, J. A., & Zhang, Y. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.10.731382

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

Bell, S., Acín‐Pérez, R., Ghouri, I. A., Meyrick, J., Lightowlers, R. N., & Russell, O. (2026) · Mitochondrion · doi:10.1016/j.mito.2026.102190

Transcriptomic and epigenetic characterization of paraventricular thalamic nucleus neurons in Polg1 mutant mice

Bagge, E. K., Kubota‐Sakashita, M., Fujimori-Tonou, N., Kasahara, T., & Kato, T. (2026) · Neuroscience Research · doi:10.1016/j.neures.2026.105089

Mitochondrial dysfunction reshapes methyl-group allocation in skeletal musclePreprint

Marmyleva, A., Tiusanen, V., Jõers, P., Sahu, B., & Suomalainen, A. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.23.746543

Mitochondrial genome instability disrupts brown adipose tissue through pseudohypoxia-iron-NAD⁺ axisPreprint

Ozturk, S. S., Pradhan, S., Lackman, M. H., Panda, L. R., Zhaivoron, A., Innilä, M., Patrício, J. S., Zacharias, L. G., Mathews, T. P., Karaman, S., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.28.747463

The role of impaired mitochondrial function in neurological manifestations of mitochondrial diseases

Brister, D., Zarate-Mendez, M., Hathazi, D., & Horváth, R. (2026) · Mammalian Genome · doi:10.1007/s00335-026-10278-5

Animal Model Selection and Deep Phenotyping in Mitochondrial Genetic Diseases: Connecting Human Variants, Multisystem Pathology, and Preclinical Evidence

Sasaki, N., & Watanabe, M. (2026) · Genes · doi:10.3390/genes17101165

Mitochondrial DNA replication and genome stability: From mechanisms to therapeutic strategies

Falkenberg, M., & Gustafsson, C. M. (2026) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2026.120241

A stress-adapted fiber state promotes clonal expansion of deleted mitochondrial DNA

Pérez‐Rodríguez, D., Rosa, I. D., Magoulopoulou, A., Ricciardi, S., Davidson, S., Lasalandra, R., Kabiljo, R., Moylett, A., Hill, T. L., Wan, T., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117995

Mitochondrial helicase Twinkle in mtDNA copy number regulation and a late-onset disease model

Tyynismaa, H. (2007) · Työväentutkimus Vuosikirja

Twinkle mutations associated with autosomal dominant progressive external ophthalmoplegia lead to impaired helicase function and in vivo mtDNA replication stalling

Goffart, S., Cooper, H. M., Tyynismaa, H., Wanrooij, S., Suomalainen, A., & Spelbrink, J. N. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddn359 · Cited by 138

Distinct Roles of the Mitochondrial DNA Helicase Twinkle in Drosophila Neurons and Muscles

Rodrigues, A. P., Goffart, S., & Oliveira, M. T. (2021) · The FASEB Journal · doi:10.1096/fasebj.2021.35.s1.02564

Human mitochondrial DNA deletions associated with mutations in the gene encoding twinkle, a phage T7 gene 4-like protein localized in mitochondria

Spelbrink, J. N., Li, F.-Y., Tiranti, V., Nikali, K., Yuan, Q.-P., Tariq, M., Wanrooij, S., Garrido, N., Comi, G., Morandi, L., et al. (2001) · Nature Genetics · doi:10.1038/90058 · Cited by 882

Twinkle and POLG defects enhance age-dependent accumulation of mutations in the control region of mtDNA

Wanrooij, S. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh634 · Cited by 127