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The Wredenberg Lab

Stockholm

About the lab

We are a research group at the Division of Molecular Metabolism at the Karolinska Institute, working on various aspects of mitochondrial biology. Mitochondria form an integral part of cellular metabolism with many metabolic pathways relying on or passing through mitochondria. Dysfunction of any of these metabolic pathways can have significant affects on human health. We are interested in understanding the connections between energy metabolism and cell function and how disturbances in this network affects an individual’s health. For this, we use a combination of model systems, ranging from the fruit fly, Drosophila melanogaster, to patient-derived iPS cells, for detailed molecular and metabolic characterisation.

Anna Wredenberg is an MD at the Centre for inherited metabolic diseases at the Karolinska University Hospital. The centre is a specialised clinic for the diagnosis of inherited metabolic diseases and performs a range of molecular, bioenergetic and metabolic investigations on patients from all over Sweden. Modern diagnostic tools have dramatically increased our understanding of these diseases, and provide a unique opportunity to identify the molecular mechanisms of metabolic derangements. We work in close collaboration with the clinic to diagnose, validate and understand metabolic diseases.


Research

Mitochondria form a dynamic network in almost every eukaryotic cell, rapidly responding to a variety of cellular demands. Although mitochondria are predominantly known to perform the final steps of aerobic energy metabolism, they are essential for other processes as diverse as steroid and lipid metabolism, iron-sulphur cluster formation, calcium buffering, reactive oxygen species (ROS) formation or apoptosis. Mitochondria are therefore seen as forming a central hub for cellular metabolism and understanding their role within the remaining metabolic network is essential for a variety of complex human diseases. For instance, mitochondrial dysfunction can be observed in several neurodegenerations, heart disease, diabetes mellitus and has been suggested to be a major contributor to the natural ageing process.

Our research tries to identify the molecular consequences of metabolic derangements, by understanding how mitochondria function within the metabolic system. We also have a special focus on understanding the turnover of mitochondrial transcripts, and how changes in mitochondrial gene expression is regulated on a post-transcriptional level.
For this we use a range of model systems, including genetically modified fruit flies, to broaden our understanding of the molecular interactions that affect mitochondrial metabolism, both in health and disease. Furthermore, integrating molecular, proteomic, and metabolic data, allows us to establish a detailed map of mitochondrial function, the dependencies of protein networks, and the metabolic consequences when things go wrong. Our connection to the clinic also allows us to confirm our findings in diseases states.

Mitochondria contain their own DNA, which is transcribed and translated within the mitochondrial network. Although several factors involved in mitochondrial RNA metabolism have already been identified, their precise function and interaction with one another is less well understood. Equally, the regulation of mitochondrial RNA processing, modification, translation, and degradation, remains largely unresolved. With the help of genetically modified fruit fly and mammalian models we study the molecular mechanisms that determine mitochondrial RNA metabolism and how they interact with mitochondrial translation.

Mitochondrial dysfunction can result in a range of rare inborn errors of metabolism (IEM), but has also been associated with a range of common diseases including cancer, heart failure, neurodegeneration, diabetes mellitus and natural ageing. The complexity and lack of understanding leaves many patients with IEMs undiagnosed. We work in close collaboration with the centre for inherited metabolic diseases at the Karolinska University Hospital to functionally validate novel gene variants identified in patients with IEM.

We combine several approaches, including analysing differentiated induced pluripotent stem (iPS) cells or mutation-specific fly models to fully validate novel genetic variants from patients with IEM. By understanding the molecular, bioenergetic and proteomic alterations in IEM, we believe that we will gain a much better understanding of human metabolism in health and disease. Additionally, by studying the proteomic and metabolic landscape of patients and animal models with mitochondrial dysfunction, we intend to develop a comprehensive co-dependency map to understand the metabolic interactions upon mitochondrial dysfunction.

The central role of mitochondria in our metabolism implies that their function can affect and be affected by a range of different metabolic pathways. In this read, alterations to the one carbon cycle, i.e. the distribution of one carbon (methyl groups) units have been identified as potential hallmarks of early mitochondrial dysfunction. Additionally, the intra-mitochondrial methylation of key factors of energy conversion links the metabolism of one carbon units and oxidative phosphorylation.

By combining animal models, with proteomic, metabolic, and molecular analysis, we study the role of intra-mitochondrial methylation potential on mitochondrial function, its role in mitochondrial RNA metabolism and translation, as well as on cellular metabolism.


PI

MD, PhD

2007 PhD Karolinska Institutet
2009 Swedish Medical Licence
2010 – 2012 PostDoc Max-Planck Institute for Biology of Ageing
2019 – Consultant in Clinical Genetics | Karolinska University Hospital
2012 – Research Group Leader | Karolinska Institutet
Anna.Wredenberg@ki.se

Anna Wredenberg
Group leader

PhD

2004 PhD University of Newcastle
2004 – 2008 PostDoc Karolinska Institutet
2008 – 2012 PostDoc Max-Planck Institute for Biology of Ageing
2012 – Karolinska University Hospital & Karolinska Institutet

Christoph.Freyer@ki.se

Christoph Freyer
Senior Scientist

PostDocs

PhD

2012 PhD Universidad Autónoma de Madrid
2012 – PostDoc Karolinska Institutet

Paula.Clemente@ki.se

Paula Clemente
Senior PostDoc

PhD

2018 PhD IBDM, Marseille
2018 – PostDoc Karolinska Institutet

Najla.ElFissi@ki.se

Najla El Fissi
Senior PostDoc

PhD

2020 PhD Iowa State University
2021- PostDoc Karolinska Institutet

kai.chang@ki.se

Kai Chang
PostDoc

PhD

2020 PhD University of Newcastle
2020 – PostDoc Karolinska Institutet

Ruth.Glasgow@ki.se

Ruth Glasgow
PostDoc

PhD

2021 PhD Univ. of Cologne, Germany
2021- PostDoc Karolinska Institutet

anastasia.rumyantseva@ki.se

Anastasia Rumyantseva
PostDoc

Students

MSc

2001 MSc Uppsala University
2001 – CMMS Karolinska University Hospital
2015 – PhD student Karolinska Institutet
Helene Bruhn
PhD student

MSc

2014 MSc Stockholm University
2014 – PhD student Karolinska Institutet
2015 – Medical student Karolinska Institutet

Isabelle.Laine@ki.se

Isabelle Laine
PhD student

Alumni

2012 – 2013     Sarah Hempenstall – PostDoc | Leiden University Medical Center | The Netherlands
2014 – 2016     Olle Dahlberg – Scientist | Karolinska University hospital | Sweden
2014 – 2018     Aleksandra Pajak – Senior Laboratory Research Scientist | The Francis Crick Institute | UK
2013 – 2021     Javier Calvo-Garrido | Scientific Advisor | Laboratorios Rovi | Madrid | Spain
2017 – 2021     David Moore |
2018 – 2022     Marco Moedas | Clinical Chemist | CMMS | Karolinska University Hospital | Sweden

2014 – 2019     Camilla Maffezzini | PostDoc | Stem Cell and Neurogenesis Unit | San Raffaele Scientific Institute | Italy
2016 – 2021     Florian Schober | PostDoc | Max-Planck Institute for Biochemistry | Martinsried | Germany
2014 – 2022     Isabelle Laine | Clinical Training | Region Stockholm | Sweden


Publications

Schober, FA.*, Tang, JX.*, Sergeant, K.*, Moedas, MF., Zierz, CM., Moore, D., Smith, C., Lewis, D., Guha, N., Hopton, S., Falkous, G., Lam, A., Pyle, A., Poulton, J., Gorman, GS., Taylor, RW:, Freyer, C.#, Wredenberg, A.#. (2022) Pathogenic SLC25A26 variants impair SAH transport activity causing mitochondrial disease. Human Molecular Genetics, ddac002

Javier Calvo-Garrido, J., Winn, D., Maffezzini, C., Wedell, A., Freyer, C., Falk, A., Wredenberg, A. (2021) Protocol for the derivation, culturing, and differentiation of human iPS-cell-derived neuroepithelial stem cells to study neural differentiation in vitro. STAR Protocols, 2(2):100528 LINK

Ferreira, CR., Rahman, S., Keller, M., Zschocke, J., ICIMD Advisory Group (2021) An international classification of inherited metabolic disorders (ICIMD). Journal of Inherited Metabolic Diseases, Vol. 44(1):164-177 LINK

Engvall, M., Kawasaki, A., Carelli, V., Wibom, R., Bruhn, H., Lesko, N., Schober, FA., Wredenberg, A., Wedell A., and Traisk F. (2021) Case Report: A Novel Mutation in the Mitochondrial MT-ND5 Gene Is Associated With Leber Hereditary Optic Neuropathy (LHON). Frontiers in Neurology, Vol. 12:652590  LINK

Stranneheim, H., Lagerstedt-Robinson, K., Magnusson, M., Kvarnung, M., Nilsson, D., Lesko, N., Engvall, M., Anderlid, B-M., Arnell, H. et al. (2021) Integration of whole genome sequencing into a health care setting: High diagnostic rates across multiple clinical entities in 3219 rare disease patients. Genome Medicine, Vol. 13:40 LINK
 
Schober, FA.*, Moore, M.*, Atanassov, I., Moedas, MF., Clemente, P., Végvári, Á., El Fissi, N., Filograna, R., Bucher, A-L., Hinze, Y., The, M., Hedman, E., Chernogubova, E., Begzati, A., Wibom, R., Jain, M., Nilsson, R., Käll, L., Wedell, A., Freyer, C.#, and Wredenberg, A.#. (2021) The One-Carbon Pool Controls Mitochondrial Energy Metabolism via Complex I and Iron-Sulfur Clusters. Science Advances Vol. 7, no. 8, eabf0717. LINK
 
Schober, FA.*, Atanassov, I.*, Moore, M., Calvo-Garrido, J., Moedas, MF., Wedell, A., Freyer, C.#, Wredenberg, A.# (2021) Direct proteome labelling in fruit flies with SILAF reveals differential phosphorylation of mitochondrial proteins upon loss of OXPHOS subunits- Molecular & Cellular Proteomics, Vol. 20:100065 LINK
 
Schober, FA., Atanassov, I., Freyer, C., Wredenberg, A. (2020) Quantitative Proteomics in Drosophila with Holidic Stable-Isotope Labeling of Amino Acids in Fruit Flies (SILAF). In: Minczuk M., Rorbach J. (eds) Mitochondrial Gene Expression. Methods in Molecular Biology, Vol. 2192:75-87 LINK
 
Correia, SP.*, Moedas,MF.*, Naess, K., Bruhn, H., Maffezzini, C., Calvo-Garrido, J., Lesko, N., Wibom, R., Schober, FA., Jemt, A., Stranneheim, H., Freyer, C., Wedell, A.#, Wredenberg, A.#. (2021) Severe congenital lactic acidosis and hypertrophic cardiomyopathy caused by an intronic variant in NDUFB7. Human Mutation, Vol. 42(2):278-384 LINK
 
Bruhn, H., Samuelsson, K., Schober, FA., Engvall, M., Lesko, N., Wibom, R., Nennesmo, I., Calvo-Garrido, J., Press, R., Stranneheim, H., Freyer, C., Wedell, A., Wredenberg, A. (2021) A novel mutation m.10372A>G in MT-ND3 causing sensorimotor axonal polyneuropathy. Neurology: Genetics, Vol. 7(2):e566 LINK
 
Cipullo, M., Pearce, SF., Lopez Sanchez, IG., Gopalakrishna, S., Krüger, A., Schober, FA., Busch, JD., Li, X., Wredenberg, A., Atanassov, I., Rorbach, J. (2021) Human GTPBP5 is involved in the late stage of mitoribosome large subunit assembly. Nucleic Acids Res. 49(1):354-370. LINK
 
Naess, K., Bruhn, H., Stranneheim, H., Freyer, C., Wibom, R., Mourier, A., Engvall, M., Nennesmo, I., Lesko, N., Wredenberg, A., Wedell, A., von Döbeln, U. (2021) Clinical Presentation, Genetic Etiology and Coenzyme Q10 Level in 55 Children with Combined Enzyme Deficiencies of the Mitochondrial Respiratory Chain. The Journal of Pediatrics. vol 228:240-251.e2
LINK

Stödberg, T.#, Magnusson, M., Lesko, N., Wredenberg, A., Martin Munoz, D., Stranneheim, H., Wedell, A.# (2020) SLC12A2 mutations cause NKCC1 deficiency with encephalopathy and impaired secretory epithelia. Neurology Genetics 6(4): e478 LINK
 
Alsina, D.*, Lytovchenko, O.*, Schab, A., Atanassov, I., Schober, FA., Jiang, M., Koolmeister, C., Wedell, A., Taylor, RW., Wredenberg, A., Larsson, N-G. (2020) FBXL 4 deficiency increases mitochondrial removal by autophagy. EMBO Mol Med. e11659 LINK
 
Maffezzini, C., Calvo-Garrido, J, Wredenberg, A.#, & Freyer, C.# (2020) Metabolic regulation of neurodifferentiation in the adult brain. Cellular and Molecular Life Sciences. LINK (Review)

Gopalakrishna, S.*, Pearce, S.F.*, Dinan, A.M., Schober, F.A., Cipullo, M., Spåhr, H., Khawaja, A., Maffezzini, C., Freyer, C., Wredenberg, A., Atanassov, I., Firth, A.E., Rorbach, J. (2019). C6orf203 is an RNA-binding protein involved in mitochondrial protein synthesis. Nucleic Acids Research. 47(17): 9386–9399 LINK
 
Pajak, A.*, Laine, I.*, Clemente, P., El-Fissi, N., Schober, F.A., Maffezzini, C., Calvo-Garrido, J., Wibom, R., Filograna, R., Dhir, A., Wedell, A., Freyer, C.#, Wredenberg, A.#. (2019). Defects of mitochondrial RNA turnover lead to the accumulation of double-stranded RNA in vivo. PLoS Genetics, 15(7): e1008240 LINK
 
Schober, F.A.*, Atanassov, I.*#, Moore, D., Wedell, A., Freyer, C.#, Wredenberg, A.# (2019) Versatile proteome labelling in fruit flies with SILAF. Preprint at: BioRxiv LINK
 
Maffezzini, C.*, Laine, I.*, Dallabona, C., Clemente, P., Calvo-Garrido, J., Wibom, R., Naess, K., Barbaro, M., Falk, A., Donnini, C., Freyer, C.#, Wredenberg, A.#, Wedell, A.# (2019) Mutations in the mitochondrial tryptophanyl-tRNA synthetase cause growth retardation and progressive leukoencephalopathy. Molecular Genetics & Genomic Medicine, 7(6)e653 LINK
 
Olivé, M.*, Engvall, M.*, Ravenscroft, G.*, Cabrera-Serrano, M., Jiao, H., Bortolotti, C.A., Pignataro, M., Lambrughi, M., Jiang, H., Forrest, A.R.R., et al. (2019). Myoglobinopathy is an adult-onset autosomal dominant myopathy with characteristic sarcoplasmic inclusions. Nature Communications, 10(1):1396 LINK
 
Calvo-Garrido, J.*, Maffezzini, C.*, Schober, F.A., Clemente, P., Uhlin, E., Kele, M., Stranneheim, H., Lesko, N., Bruhn, B., Svenningsson, P., Falk, A., Wedell, A., Freyer, C.#, Wredenberg, A.#. (2019). SQSTM1/p62-directed metabolic reprogramming is essential for normal neurodifferentiation. Stem Cell Reports, 12(4):p696-711 LINK
 
Filograna, R., Koolmeister, C., Upadhyay, M., Pajak, A., Clemente, P., Wibom, R., Simard, M.L., Wredenberg, A., Freyer, C., Stewart, J.B., Larsson, N.-G. (2019). Modulation of mtDNA copy number ameliorates the pathological consequences of a heteroplasmic mtDNA mutation in the mouse. Science Advances, 5(4):eaav9824 LINK
 
Katsu-Jiménez, Y., Vázquez-Calvo, C., Maffezzini, C., Halldin, M., Peng, X., Freyer, C., Wredenberg, A., Giménez-Cassina, A., Wedell, A., Arnér, E.S.J. (2019). Absence of TXNIP in humans leads to lactic acidosis and low serum methionine linked to deficient respiration on pyruvate. Diabetes, 68(4):709-723 LINK

Richter, U., Evans, M.E., Clark, W.C., Marttinen, P., Shoubridge, E.A., Suomalainen, A., Wredenberg, A., Wedell, A., Pan, T., Battersby, B.J. (2018) RNA modification landscape of the human mitochondrial tRNALys regulates protein synthesis. Nature Communications, 9(1):3966 LINK
 
Paucar, M., Pajak, A., Freyer, C., Bergendal, Å., Döry, M., Laffita-Mesa, J.M., Stranneheim, H., Lagerstedt-Robinson, K., Savitcheva, I., Walker, R.H., Wedell, A., Wredenberg, A., Svenningsson, P. (2018) Chorea, psychosis, acanthocytosis, and prolonged survival associated with ELAC2 mutations. Neurology, pii:10.1212/WNL.0000000000006320 LINK
 
Herebian, D., Seibt, A., Smits, S.H.J., Bünning, G., Freyer, C., Prokisch, H., Karall, D., Wredenberg, A., Wedell, A., López, L.C., Mayatepek, E., Distelmaier, F. (2017) Detection of 6-demethoxyubiquinone in CoQ10 deficiency disorders: Insights into enzyme interactions and identification of potential therapeutics. Mol Genet Metab. 2017 Jul;121(3):216-223. LINK
 
Siibak, T.*, Clemente, P.*, Bratic, A., Bruhn, H., Kauppila, T.E.S., Macao, B., Schober, F.A., Lesko, N., Wibom, R., Naess, K., Nennesmo, I., Wedell, A., Peter, B., Freyer, C., Falkenberg, M.#, Wredenberg, A.# (2017) A multi-systemic mitochondrial disorder due to a dominant p.Y955H disease variant in DNA polymerase gamma. Hum Mol Genet. 2017 Jul 1;26(13):2515-2525.
 
Tegelberg, S., Tomašić, N., Kallijärvi, J., Purhonen, J., Elmér, E., Lindberg, E., Nord, D.G., Soller, M., Lesko, N., Wedell, A., Bruhn, H., Freyer, C., Stranneheim, H., Wibom, R., Nennesmo, I., Wredenberg, A., Eklund, E.A., Fellman, V. (2017) Respiratory chain complex III deficiency due to mutated BCS1L: a novel phenotype with encephalomyopathy, partially phenocopied in a Bcs1l mutant mouse model. Orphanet J Rare Dis. 2017 Apr 20;12(1):73.
 
Haack TB, Ignatius E, Calvo-Garrido J, Iuso A, Isohanni P, Maffezzini C, Lönnqvist T, Suomalainen A, Gorza M, Kremer LS, Graf E, Hartig M, Berutti R, Paucar M, Svenningsson P, Stranneheim H, Brandberg G, Wedell A, Kurian MA, Hayflick SA, Venco P, Tiranti V, Strom TM, Dichgans M, Horvath R, Holinski-Feder E, Freyer C, Meitinger T, Prokisch H, Senderek J, Wredenberg A, Carroll CJ, Klopstock T. (2016) Absence of the Autophagy Adaptor SQSTM1/p62 Causes Childhood-Onset Neurodegeneration with Ataxia, Dystonia, and Gaze Palsy. Am J Hum Genet. 2016 Sep 1;99(3):735-743. LINK
 
Bratic A, Clemente P, Calvo-Garrido J, Maffezzini C, Felser A, Wibom R, Wedell A, Freyer C, Wredenberg A. (2016) Mitochondrial Polyadenylation Is a One-Step Process Required for mRNA Integrity and tRNA Maturation. PLoS Genet. 2016 May 13;12(5):e1006028.
 
Bratic A, Kauppila TE, Macao B, Grönke S, Siibak T, Stewart JB, Baggio F, Dols J, Partridge L, Falkenberg M, Wredenberg A, Larsson NG. (2015) Complementation between polymerase- and exonuclease-deficient mitochondrial DNA polymerase mutants in genomically engineered flies. Nat Commun. 2015 Nov 10;6:8808.
 
Kishita Y, Pajak A, Bolar NA, Marobbio CM, Maffezzini C, Miniero DV, Monné M, Kohda M, Stranneheim H, Murayama K, Naess K, Lesko N, Bruhn H, Mourier A, Wibom R, Nennesmo I, Jespers A, Govaert P, Ohtake A, Van Laer L, Loeys BL, Freyer C, Palmieri F, Wredenberg A, Okazaki Y, Wedell A. (2015) Intra-mitochondrial Methylation Deficiency Due to Mutations in SLC25A26. Am J Hum Genet. 2015 Nov 5;97(5):761-8.
 
Gineste C, Hernandez A, Ivarsson N, Cheng AJ, Naess K, Wibom R, Lesko N, Bruhn H, Wedell A, Freyer C, Zhang SJ, Carlström M, Lanner JT, Andersson DC, Bruton JD, Wredenberg A, Westerblad H. (2015) Cyclophilin D, a target for counteracting skeletal muscle dysfunction in mitochondrial myopathy. Hum Mol Genet. 2015 Dec 1;24(23):6580-7.
 
Clemente P, Pajak A, Laine I, Wibom R, Wedell A, Freyer C, Wredenberg A. (2015) SUV3 helicase is required for correct processing of mitochondrial transcripts.
Nucleic Acids Res. 2015 Sep 3;43(15):7398-413.
 
Freyer C, Stranneheim H, Naess K, Mourier A, Felser A, Maffezzini C, Lesko N, Bruhn H, Engvall M, Wibom R, Barbaro M, Hinze Y, Magnusson M, Andeer R, Zetterström RH, von Döbeln U, Wredenberg A, Wedell A. (2015) Rescue of primary ubiquinone deficiency due to a novel COQ7 defect using 2,4-dihydroxybensoic acid. J Med Genet. 2015 Nov;52(11):779-83.
 
Stranneheim H, Engvall M, Naess K, Lesko N, Larsson P, Dahlberg M, Andeer R, Wredenberg A, Freyer C, Barbaro M, Bruhn H, Emahazion T, Magnusson M, Wibom R, Zetterström RH, Wirta V, von Döbeln U, Wedell A. (2014) Rapid pulsed whole genome sequencing for comprehensive acute diagnostics of inborn errors of metabolism. BMC Genomics. 2014 Dec 11;15(1):1090.
Acuna-Hidalgo R, Schanze D, Kariminejad A, Nordgren A, Kariminejad MH, Conner P, Grigelioniene G, Nilsson D, Nordenskjöld M, Wedell A, Freyer C, Wredenberg A, Wieczorek D, Gillessen-Kaesbach G, Kayserili H, Elcioglu N, Ghaderi-Sohi S, Goodarzi P, Setayesh H, van de Vorst M, Steehouwer M, Pfundt R, Krabichler B, Curry C, MacKenzie MG, Boycott KM, Gilissen C, Janecke AR, Hoischen A, Zenker M. (2014) Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway. Am J Hum Genet. 2014 Sep 4;95(3):285-93.
 
Wredenberg, A.*, Lagouge, M.*, Bratic, A.*, Metodiev, M.D., Spåhr, H., Mourier, A., Freyer, C., Ruzzenente, B., Tain, L., Grönke, S., Baggio, F., Kukat, C., Kremmer, E., Wibom, R., Polosa, P.L., Habermann, B., Partridge, L., Park, C.B., Larsson, N.-G. (2013) MTERF3 regulates mitochondrial ribosome biogenesis in invertebrates and mammals. PLoS Genet. 2013;9(1):e1003178. LINK
Freyer, C., Clemente, P. & Wredenberg, A. Mitochondrial RNA Turnover in Metazoa. in RNA Metabolism in Mitochondria (eds. Cruz-Reyes, J. & Gray, M. W.) 17–46 (Springer International Publishing, 2018). LINK
 
Hagström, E., Freyer, C., Battersby, B.J., Stewart, J.B., & Larsson, N.-G. (2013). No recombination of mtDNA after heteroplasmy. Nucleic Acids Research, 42(2): 1111-1116. LINK

Milenkovic, D., Matic, S., Kühl, I., Ruzzenente, B., Freyer, C., Jemt, E., et al. (2013). TWINKLE is an essential mitochon- drial helicase required for synthesis of nascent D-loop strands and complete mtDNA replication. Human Molecular Genetics, 22(10): 1983–1993. LINK

Ross, J.M.*, Stewart, J.B.*, Hagström, E., Brené, S., Mourier, A., Coppotelli, G., Freyer, C., et al. (2013). Germline mito- chondrial DNA mutations aggravate ageing and can impair brain development. Nature, 501(7467): 412-415. LINK

Freyer, C., Cree, L.M., Mourier, A., Stewart, J.B., Koolmeister, C., Milenkovic, D., et al. (2012). Variation in germline mtDNA heteroplasmy is determined prenatally but modified during subsequent transmission. Nature Genetics, 44(11): 1282–1285. LINK
 
Ruzzenente, B., Metodiev, M.D., Wredenberg, A., Bratic, A., Park, C.B., Cámara, Y., et al. (2012). LRPPRC is necessary for polyadenylation and coordination of translation of mitochondrial mRNAs. The EMBO Journal, 31(2): 443–456. LINK
 
Ameur, A.*, Stewart, J.B.*, Freyer, C., Hagström, E., Ingman, M., Larsson, N.-G., & Gyllensten, U. (2011). Ultra-deep sequencing of mouse mitochondrial DNA: mutational patterns and their origins. PLoS Genetics, 7(3): e1002028. LINK
 
Bratic, A.*, Wredenberg, A.*, Grönke, S., Stewart, J.B., Mourier, A., Ruzzenente, B., et al. (2011). The bicoid stability factor controls polyadenylation and expression of specific mitochondrial mRNAs in Drosophila melanogaster. PLoS Genetics, 7(10): e1002324. LINK
 
Freyer, C., Park, C.B., Ekstrand, M., Shi, Y., Khvorostova, J., Wibom, R., et al. (2010). Maintenance of respiratory chain function in mouse hearts with severely impaired mtDNA transcription. Nucleic Acids Research, 38(19): 6577–6588. LINK
 
Aydin, J., Andersson, D.C., Hänninen, S. L., Wredenberg, A., Tavi, P., Park, C.B., et al. (2009). Increased mitochondrial Ca2+ and decreased sarcoplasmic reticulum Ca2+ in mitochondrial myopathy. Human Molecular Genetics, 18(2): 278–288. LINK
 
Edgar, D.*, Shabalina, I.G.*, Cámara, Y., Wredenberg, A., Calvaruso, M.A., Nijtmans, L., et al. (2009). Random point mutations with major effects on protein-coding genes are the driving force behind premature aging in mtDNA mutator mice. Cell Metabolism, 10(2): 131–138. LINK
 
Naess, K., Freyer, C., Bruhn, H., Wibom, R., Malm, G., Nennesmo, I., et al. (2009). MtDNA mutations are a common cause of severe disease phenotypes in children with Leigh syndrome. Biochimica Et Biophysica Acta, 1787(5): 484–490. LINK
 
Stewart, J.B., Freyer, C., Elson, J.L., & Larsson, N.-G. (2008a). Purifying selection of mtDNA and its implications for understanding evolution and mitochondrial disease. Nature Reviews. Genetics, 9(9), 657–662. LINK
 
Stewart, J.B., Freyer, C., Elson, J.L., Wredenberg, A., Cansu, Z., Trifunovic, A., & Larsson, N.-G. (2008b). Strong purifying selection in transmission of mammalian mitochondrial DNA. PLoS Biology, 6(1): e10. LINK
 
Freyer, C., & Larsson, N.-G. (2007). Is energy deficiency good in moderation? Cell, 131(3): 448–450. LINK
 
Wredenberg, A., Freyer, C., Sandström, M.E., Katz, A., Wibom, R., Westerblad, H., & Larsson, N.-G. (2006). Respiratory chain dysfunction in skeletal muscle does not cause insulin resistance. Biochemical and Biophysical Research Communications, 350(1): 202–207. LINK
 
Trifunovic, A., Hansson, A., Wredenberg, A., Rovio, A.T., Dufour, E., Khvorostov, I., et al. (2005). Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production., 102(50): 17993–17998. LINK
 
Trifunovic, A., Wredenberg, A., Falkenberg, M., Spelbrink, J.N., Rovio, A.T., Bruder, C.E., et al. (2004). Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature, 429(6990): 417–423. LINK
 
Wredenberg, A., Wibom, R., Wilhelmsson, H., Graff, C., Wiener, H.H., Burden, S.J., et al. (2002). Increased mitochondrial mass in mitochondrial myopathy mice. Proceedings of the National Academy of Sciences of the United States of America, 99(23), 15066–15071. LINK
 
Graff, C., Wredenberg, A., Silva, J.P., Bui, T.H., Borg, K., & Larsson, N.-G. (2000). Complex genetic counselling and prenatal analysis in a woman with external ophthalmoplegia and deleted mtDNA. Prenatal Diagnosis, 20(5): 426–431.
 
Tollbäck, A., Eriksson, S., Wredenberg, A., Jenner, G., Vargas, R., Borg, K., & Ansved, T. (1999). Effects of high resistance training in patients with myotonic dystrophy. Scandinavian Journal of Rehabilitation Medicine, 31(1): 9–16.


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Karolinska Institutet
Division of Molecular Metabolism
Dept. of Medical Biochemistry & Biophysics
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