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. One of our interests is understanding the role of the mitochondrial methylation potential on mitochondrial function and how it affects the cellular one carbon metabolism and cell function. 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 fly or mouse models, 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. For instance, mitochondrial transcription results in the formation of long, polycistronic transcripts that need to be cleaved and modified for maturation. Four decades ago, the tRNA punctuation model proposed a mechanism for this processing, and the responsible factors and structures have since been identified. But not all mtDNA-encoded genes are separated by tRNAs, and their processing mechanism remained unknown. We recently demonstrated that cleavage of these non-canonical transcripts results in the formation of 3′ terminal phosphate groups, which are hydrolysed by the mitochondrial phosphatase ANGEL2. Further, we proposed that members of the FASTKD family are responsible for the cleavage, thus presenting a mechanism for non-canonical processing in mitochondria.
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. We are currently investigating whether untargeted proteomics can be used to diagnose patients with mitochondrial dysfunction of unknown cause.
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. We recently presented a comprehensive mitochondrial methylproteome in fly, mouse and human. Furthermore, our work suggests that a substantial amount of methylation modification of mitochondrial proteins occurs prior to protein import, and we were able to link one carbon and energy metabolism via cytosolic and mitochondrial S-adenosylmethionine (SAM) levels. We are currently exploring to what extend the mitochondrial methylation potential affects cellular metabolism in a variety of tissues.
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
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
PostDocs
PhD
2021 PhD Univ. of Cologne, Germany
2021- PostDoc Karolinska Institutet
MD, PhD
2020 – Medical Doctor Karolinska Institutet
2022 – PhD Karolinska Institutet
Students
MSc
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 | Associate Consultant | Oxford Pharmagenesis | UK
2018 – 2022 Marco Moedas | Clinical Chemist | CMMS | Karolinska University Hospital | Sweden
2012 – 2022 Paula Clemente | Senior Scientist | Universidad Autónoma de Madrid | Spain
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
Zhang J, Koolmeister C, Han J, Filograna R, Hanke L, Àdori M, Sheward DJ, Teifel S, Gopalakrishna S, Shao Q, Liu Y, Zhu K, Harris RA, McInerney G, Murrell B, Aoun M, Bäckdahl L, Holmdahl R, Pekalski M, Wedell A, Engvall M, Wredenberg A, Karlsson Hedestam GB, Castro Dopico X, Rorbach J. (2023) Antigen receptor stimulation induces purifying selection against pathogenic mitochondrial tRNA mutations. JCI Insight 8(17):e167656 LINK
Erdinc D, Macao B, Valenzuela S, Lesko N, Naess K, Peter B, Bruhn H, Wedell A, Wredenberg A#, Falkenberg M#. (2023) The disease-causing mutation p.F907I reveals a novel pathogenic mechanism for POLγ-related diseases. Biochim Biophys Acta Mol Basis Dis. 1869(7):166786. LINK
Mattison KA, Tossing G, Mulroe F, Simmons C, Butler KM, Schreiber A, Alsadah A, Neilson DE, Naess K, Wedell A, Wredenberg A, Sorlin A, McCann E, Burghel GJ, et al. (2023) ATP6V0C variants impair V-ATPase function causing a neuro-developmental disorder often associated with epilepsy. Brain 146(4):1357-1372 LINK
Vaz R, Wincent J, Elfissi N, Rosengren Forsblad K, Pettersson M, Naess K, Wedell A, Wredenberg A, Lindstrand A, Ygberg S. (2022) A Missense Variant in PDK1 Associated with Severe Neurodevelopmental Delay and Epilepsy. Biomedicines. 10(12):3171. LINK
Clemente P#, Calvo-Garrido J, Pearce SF, Schober FA, Shigematsu M, Siira SJ, Laine I, Spåhr H, Steinmetzger C, Petzold K, Kirino Y, Wibom R, Packham O, Filipovska A, Rorbach J, Freyer C#, Wrednebrg A#. (2022) ANGEL2 phosphatase activity is required for non-canonical mitochondrial RNA processing. Nat Commun 13, 5750 LINK
Misic J, Milenkovic D, Al-Behadili A, Xie X, Jiang M, Jiang S, Filograna R, Koolmeister C, Siira SJ, Jenninger L, Filipovska A, Clausen AR, Caporali L, Valentino ML, La Morgia C, Carelli V, Nicholls TJ, Wredenberg A, Falkenberg M, Larsson NG. (2022) Mammalian RNase H1 directs RNA primer formation for mtDNA replication initiation and is also necessary for mtDNA replication completion. Nucleic Acids Res. 50(15):8749-8766 LINK
Rosenhahn E*, O’Brien TJ*, Zaki MS, Sorge I, Wieczorek D, Rostasy K, Vitobello A, Nambot S, Alkuraya FS, Hashem MO, et al. (2022) Bi-allelic loss-of-function variants in PPFIBP1 cause a neurodevelopmental disorder with microcephaly, epilepsy, and periventricular calcifications. Am J Hum Genet. 109(8):1421-1435 LINK
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
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