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Prof. Kari Majamaa's Group Research Project "Northern Mitochondria" MITOCHONDRIAL DNA MUTATIONS AS CAUSES AND POLYMORPHISMS AS RISK FACTORS FOR DESEASES PROJECT Mitochondrial diseases are a clinically variable group of disorders that are characterized by disturbances in cellular energy metabolism and structural disturbances of the mitochondria. The first mutations in mitochondrial DNA were found in 1988, and, since then, mitochondrial genetics has become one of the main avenues of molecular research in neurology. The aim of the research project Northern Mitochondria is to study the molecular etiology, molecular epidemiology, biochemical pathophysiology and clinical features of these disorders.
Molecular epidemiology of mitochondrial diseases has been the main subject of the project. The clinical entities involved include various neurological diseases, diabetes mellitus and sensorineural hearing impairment. Mitochondrial population genetics has evolved to be part of the project and currently Northern Mitochondria is well prepared for the new field of mitochondrial genomics. Clinical studies have been performed in collaboration with specialists in many clinical disciplines to resolve the phenotype of mitochondrial DNA mutations in population-based cohorts. Finally, the biochemical consequences of mtDNA mutations have been studied in cultured cells.  In this project we carry out:                                                                        1. molecular research on mitochondrial DNA, mitochondrial genomics, in order to identify disease-causing mutations and polymorphisms that increase disease susceptibility,  2. biochemical research on mitochondrial respiratory chain and morphological studies on cultured cells in order to detect the consequences of those mutations  3. clinical research in order to evaluate the clinical pathophysiology of the mutations.
PEOPLE Project leader Kari Majamaa, MD, PhD, professor of neurology Senior collaborators Johanna Uusimaa, MD, PhD Anne Remes, MD, PhD Marko Kervinen, MD, PhD Jukka Moilanen, MD, PhD Postdoctoral investigators Reetta Hinttala, PhD Mikko Kärppä, MD, PhD Harri Rusanen, MD, PhD Johanna Annunen-Rasila, MD, PhD PhD students Anna-Leena Heula, MD Sanna Häkli, MD Jukka Kiiskilä, MSc, BM Laura Kytövuori, MSc Maria Lehtilahti, MD Taija Pihlajaniemi, DDS Allan Seppänen, MD Ari Siitonen, MSc, BM Heidi Soini, MSc Susanna Ylönen, MSc Graduate students Joonas Lipponen, Medical student Antti Väisänen, BSc Laboratory technicians Anja Heikkinen Pirjo Keränen COLLABORATORS Collaborators at the University Hospital and University of Oulu Department of Neurology Department of Pediatrics Department of Biochemistry Department of Internal Medicine Department of Otorhinolaryngology Collaborators at other universities University of Turku University of Kuopio University of Gothenburg (Sweden)
RELEVANT PUBLICATIONS Hinttala R, Kervinen M, Uusimaa J, Maliniemi P, Finnilä S, Rantala H, Remes AM, Hassinen IE, Majamaa K: Analysis of functional consequences of haplogroup J polymorphisms m.4216T>C and m.3866T>C in human MT-ND1. Mutagenesis of homologous positions in Escherichia coli. Mitochondrion 10: 358-361, 2010. Lindroos MM, Borra R, Parkkola R, Virtanen S, Lepomäki V, Bucci M, Virta JR, Rinne J, Nuutila P, Majamaa K: Cerebral oxygen and glucose metabolism in patients with mitochondrial m.3243A>G mutation. Brain 132: 3274-3284, 2009. Uusimaa J, Moilanen JS, Vainionpää L, Tapanainen P, Lindholm P, Nuutinen M, Löppönen T, Mäki-Torkko E, Rantala H, Majamaa K: Prevalence, segregation and phenotype of the mtDNA 3243A>G mutation in children. Ann Neurol 62: 278-287, 2007. Annunen-Rasila J, Ohlmeier S, Tuokko H, Veijola J, Majamaa K: Proteome and cytoskeleton responses in osteosarcoma cells with reduced OXPHOS activity. Proteomics 7: 2189-2200, 2007. Kervinen M, Hinttala R, Helander HM, Kurki S, Uusimaa J, Finel M, Majamaa K, Hassinen IE: The MELAS mutations 3946 and 3949 perturb the critical structure in a conserved loop of the ND1 subunit of mitochondrial Complex I. Hum Mol Genet 15: 2543-2552, 2006. Niemi AK, Moilanen JS, Tanaka M, Hervonen A, Hurme M, Lehtimäki T, Arai Y, Hirose N, Majamaa K: A combination of three common inherited mitochondrial DNA polymorphisms promotes longevity in Finnish and Japanese subjects. Eur J Hum Genet 13: 166-170, 2005. Kärppä M, Herva R, Moslemi AR, Oldfors A, Kakko S, Majamaa K: Spectrum of myopathic findings in 50 patients with the 3243A>G mutation in mitochondrial DNA. Brain 128: 1861-1869, 2005. Moilanen JS, Majamaa K: Phylogenetic network and physicochemical properties of nonsynonymous mutations in the protein-coding genes of human mitochondrial DNA. Mol Biol Evol 20: 1195-1210, 2003. Finnilä S, Lehtonen MS, Majamaa K: Phylogenetic network for European mitochondrial DNA. Am J Hum Genet 68: 1475-1484, 2001. Majamaa K, Moilanen JS, Uimonen S, Remes AM, Salmela PI, Kärppä M, Majamaa-Voltti KAM, Rusanen H, Sorri M, Peuhkurinen KJ, Hassinen IE: Epidemiology of A3243G, the mutation for mitochondrial encephalomyopathy, Lactic Acidosis, and strokelike episodes: Prevalence of the mutation in an adult population. Am J Hum Genet 63: 447-454, 1998. Majamaa K, Finnilä S, Turkka J, Hassinen IE: Mitochondrial haplogroup U as a risk factor for occipital stroke in migraine. Lancet 352: 455-456, 1998.