The Wredenberg Lab


About the lab

We are a young 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 recently received an ERC start-up grant. She is a Ragnar Söderberg fellow in Medicine and 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.


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.

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.
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.

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, the mechanisms of what regulates their involvement in processing, modifying or degrading are still very sparse. With the help of genetically modified fruit fly 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.


Anna Wredenberg


2007 PhD Karolinska Institutet
2009 Swedish Medical Licence
2010 – 2012 PostDoc Max-Planck Institute for Biology of Ageing
2012 – Resident Clinical Genetics | Karolinska University Hospital
2012 – Research Group Leader | Karolinska Institutet

Anna Wredenberg
Group leader
Christoph Freyer


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
Senior Scientist


Paula Clemente


2012 PhD Universidad Autónoma de Madrid
2012 – PostDoc Karolinska Institutet


Paula Clemente
Senior PostDoc
Aleksandra Pajak


2013 PhD University of Newcastle
2013 PostDoc Okayama University
2014 – PostDoc Karolinska Institutet


Aleksandra Pajak
Version 2


2011 PhD Universidad Autónoma de Madrid
2012 – PostDoc Karolinska Institutet


Javier Calvo Garrido
David Moore


2017 PhD University of Newcastle
2017 – PostDoc Karolinska Institutet



David Moore


Camilla Maffezzini


2014 MSc University of Pavia
2014 – PhD student Karolinska Institutet


Camilla Maffezzini
PhD student
Isabelle Laine


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


Isabelle Laine
PhD student
Florian Schober


2015 MSc Karolinska Institutet
2016 – PhD student Karolinska Institutet


Florian Schober
PhD student
Helene Bruhn


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


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. Molecular Genetics and Metabolism, 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. Human Molecular Genetics, 26 (13): 2515-2525 LINK
Tegelberg, S.*, Tomašić, N.*, Kallijärvi, J., Purhonen, J., Elmér, E., Lindberg, E., Gisselsson-Nord, D., 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 Journal of Rare Diseases, 12(1): 73 LINK

Kauppila, J.H.K.*, Baines, H.L.*, Bratic, A., Simard, M.-L., Freyer, C., Mourier, A., Stamp, C., Filograna, R., Larsson, N.-G.#, Greaves, L.C.#, & Stewart, J.B.#. (2016). A phenotype-driven approach to generate mouse models with pathogenic mtDNA mutations causing mitochondrial disease. Cell Reports, 16(11): 2980-2990. LINK
Haack, T.B.*#, Ignatius, E.*, Calvo-Garrido, J.*, Iuso, A.*, Isohanni, P., Maffezzini, C., Lönnqvist, T., Suomalainen, A., Gorza, M., Kremer,L.S., Graf, E., Hartig, M., Berutti, R., Arce, M.P., Svenningsson, P., Stranneheim, H., Brandberg, G., Wedell, A., Kurian, M.A., Hayflick, S.A., Venco, P., Tiranti, V., Strom, T.M., Dichgans, M., Horvath, R., Holinski-Feder, E., Freyer, C., Meitinger, T., Prokisch, H.#, Senderek, J.#, Wredenberg, A.#, Carroll, C.J.#, & Klopstock, T.#. (2016). Absence of the Autophagy Adaptor SQSTM1/p62 Causes Childhood-Onset Neurodegeneration with Ataxia, Dystonia, and Gaze Palsy. American Journal of Human Genetics, 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 Genetics, 12(5): e1006028. LINK

Gineste, C., Hernandez, A., Ivarsson, N., Cheng, A.J., Naess, K., Wibom, R., Lesko, N., Bruhn, H., Wedell, A., Freyer, C., Zhang, S.-J., Carlström, M., Lanner, J.T., Andersson, D.C., Bruton, J.D., Wredenberg, A.#, & Westerblad, H#. (2015). Cyclophilin D, a target for counteracting skeletal muscle dysfunction in mitochondrial myopathy. Human Molecular Genetics, 24(23): 6580-6587. LINK
Jemt, E., Persson, Ö., Shi, Y., Mehmedovic, M., Uhler, J.P., Dávila López, M., Freyer, C., et al. (2015). Regulation of DNA replication at the end of the mitochondrial D-loop involves the helicase TWINKLE and a conserved sequence element. Nucleic Acids Research, 43(19): 9262-9275. LINK
Bratic, A., Kauppila, T.E.S., Macao, B., Grönke, S., Siibak, T., Stewart, J.B., Baggio, F., Dols, J., Partridge, L., Falkenberg, M., Wredenberg, A.#, & Larsson, N.-G.# (2015). Complementation between polymerase- and exonuclease-deficient mitochondrial DNA polymerase mutants in genomically engineered flies. Nature Communications, 6: 8808. LINK
Clemente, P., Pajak, A., Laine, I., Wibom, R., Wedell, A., Freyer, C.#, & Wredenberg, A#. (2015). SUV3 helicase is requiredfor correct processing of mitochondrial transcripts. Nucleic Acids Research, 43(15): 7398–7413. LINK
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, R.H., von Döbeln, U., Wredenberg, A.#, & Wedell, A.# (2015). Rescue of primary ubiquinone deficiency due to a novel COQ7 defect using 2,4-dihydroxybensoic acid. Journal of Medical Genetics, 52(11): 779–783. LINK
Kishita, Y.*, Pajak, A.*, Bolar, N.A*., Marobbio, C.M.T.*, Maffezzini, C., Miniero, D.V., 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, B.L., Freyer, C., Palmieri, F.#, Wredenberg, A.#, Okazaki, Y.#, & Wedell, A.# (2015). Intra-mitochondrial Methylation Deficiency Due to Mutations in SLC25A26. American Journal of Human Genetics, 97(5): 761–768. LINK

Acuna-Hidalgo, R., Schanze, D., Kariminejad, A., Nordgren, A., Kariminejad, M.H., Conner, P., Grigelioniene , G., Nilsson, D., Nordenskjöld , M., Wedell, A., Freyer, C., Wredenberg, A., et al. (2014). Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway. American Journal of Human Genetics, 95(3): 285–293. LINK

Stranneheim, H., Engvall, M., Naess, K., Lesko, N., Larsson, P., Dahlberg, M., Andeer, R., Wredenberg, A., Freyer, C., et al. (2014). Rapid pulsed whole genome sequencing for comprehensive acute diagnostics of inborn errors of metabolism. BMC Genomics, 15(1): 1090. LINK

Wredenberg, A.*, Lagouge, M.*, Bratic, A.*, Metodiev, M.D., Spåhr, H., Mourier, A., et al. (2013). MTERF3 regulates mitochondrial ribosome biogenesis in invertebrates and mammals. PLoS Genetics, 9(1): e1003178. 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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+46 (0)8 524 830 37
Karolinska Institutet
Division of Molecular Metabolism
Dept. of Medical Biochemistry & Biophysics
Retziusväg 8 | 171 77 Stockholm | Sweden
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