Kishita 2015 Am J Hum Genet
Kishita Y, Pajak A, Bolar NA, Marobbio CM, Maffezzini C, Miniero DV, MonnΓ© 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 97:761-8. |
Kishita Y, Pajak A, Bolar NA, Marobbio CM, Maffezzini C, Miniero DV, Monne 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) Am J Hum Genet
Abstract: S-adenosylmethionine (SAM) is the predominant methyl group donor and has a large spectrum of target substrates. As such, it is essential for nearly all biological methylation reactions. SAM is synthesized by methionine adenosyltransferase from methionine and ATP in the cytoplasm and subsequently distributed throughout the different cellular compartments, including mitochondria, where methylation is mostly required for nucleic-acid modifications and respiratory-chain function. We report a syndrome in three families affected by reduced intra-mitochondrial methylation caused by recessive mutations in the gene encoding the only known mitochondrial SAM transporter, SLC25A26. Clinical findings ranged from neonatal mortality resulting from respiratory insufficiency and hydrops to childhood acute episodes of cardiopulmonary failure and slowly progressive muscle weakness. We show that SLC25A26 mutations cause various mitochondrial defects, including those affecting RNA stability, protein modification, mitochondrial translation, and the biosynthesis of CoQ10 and lipoic acid. β’ Keywords: S-adenosylmethionine, SAM, SLC25A26, Methylation, Mitochondria, Mitochondrial dysfunction
Labels: MiParea: Respiration, Patients
Pathology: Inherited, Other
Organism: Human Tissue;cell: Skeletal muscle
Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase
Coupling state: OXPHOS, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.
HRR: Oxygraph-2k
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