{"entity": "researcher", "timestamp": "2026-08-13T18:15:01.156Z", "family": "Freyer", "given": "Christoph", "initials": "C", "orcid": "0000-0003-0418-1673", "affiliations": ["Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden.", "Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.", "Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Karolinska Institutet, Stockholm, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/888298d25fb94acca7639063d3592373.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/888298d25fb94acca7639063d3592373"}}, "publications": [{"entity": "publication", "iuid": "9f05d86339b84c169856faace9e38db9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9f05d86339b84c169856faace9e38db9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9f05d86339b84c169856faace9e38db9"}}, "title": "The mitochondrial methylation potential gates mitoribosome assembly.", "authors": [{"family": "Glasgow", "given": "Ruth I C", "initials": "RIC"}, {"family": "Singh", "given": "Vivek", "initials": "V", "orcid": "0000-0003-4656-3362", "researcher": {"href": "https://publications.scilifelab.se/researcher/0576b8ffc93d42f6b47d9d0d7d01bbd0.json"}}, {"family": "Pe\u00f1a-P\u00e9rez", "given": "Luc\u00eda", "initials": "L", "orcid": "0000-0002-5044-7754", "researcher": {"href": "https://publications.scilifelab.se/researcher/111f8a8c4c6d4d2ea60e5fc76831b7fa.json"}}, {"family": "Wilhalm", "given": "Alissa", "initials": "A"}, {"family": "Moedas", "given": "Marco F", "initials": "MF"}, {"family": "Moore", "given": "David", "initials": "D"}, {"family": "Rosenberger", "given": "Florian A", "initials": "FA", "orcid": "0000-0003-4604-6170", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e9cd9d0742d40e3b5dc1abfde64d5c4.json"}}, {"family": "Li", "given": "Xinping", "initials": "X"}, {"family": "Atanassov", "given": "Ilian", "initials": "I", "orcid": "0000-0001-8259-2545", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8d22eab41e44364be8966abaf693de1.json"}}, {"family": "Saba", "given": "Mira", "initials": "M"}, {"family": "Cipullo", "given": "Miriam", "initials": "M"}, {"family": "Rorbach", "given": "Joanna", "initials": "J", "orcid": "0000-0002-2891-2840", "researcher": {"href": "https://publications.scilifelab.se/researcher/a069374613a7403b818ce7ca400f3627.json"}}, {"family": "Wedell", "given": "Anna", "initials": "A"}, {"family": "Freyer", "given": "Christoph", "initials": "C", "orcid": "0000-0003-0418-1673", "researcher": {"href": "https://publications.scilifelab.se/researcher/888298d25fb94acca7639063d3592373.json"}}, {"family": "Amunts", "given": "Alexey", "initials": "A", "orcid": "0000-0002-5302-1740", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7d0bf36ad1a47f5b5b88f78d1e15395.json"}}, {"family": "Wredenberg", "given": "Anna", "initials": "A", "orcid": "0000-0002-2500-6121", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ea9ee7305424cdb8c238ef569e5be03.json"}}], "type": "journal article", "published": "2025-06-25", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "16", "issue": "1", "pages": "5388"}, "abstract": "S-adenosylmethionine (SAM) is the principal methyl donor in cells and is essential for mitochondrial gene expression, influencing RNA modifications, translation, and ribosome biogenesis. Using direct long-read RNA sequencing in mouse tissues and embryonic fibroblasts, we show that processing of the mitochondrial ribosomal gene cluster fails in the absence of mitochondrial SAM, leading to an accumulation of unprocessed precursors. Proteomic analysis of ribosome fractions revealed these precursors associated with processing and assembly factors, indicating stalled biogenesis. Structural analysis by cryo-electron microscopy demonstrated that SAM-dependent methylation is required for peptidyl transferase centre formation during mitoribosome assembly. Our findings identify a critical role for SAM in coordinating mitoribosomal RNA processing and large subunit maturation, linking cellular methylation potential to mitochondrial translation capacity.", "doi": "10.1038/s41467-025-60977-x", "pmid": "40562754", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "NGI Long read": "Service", "Bioinformatics Support for Computational Resources": "Service", "NGI Stockholm (Genomics Applications)": null}, "xrefs": [{"db": "pmc", "key": "PMC12198368"}, {"db": "pii", "key": "10.1038/s41467-025-60977-x"}], "notes": [], "created": "2025-08-19T13:45:26.954Z", "modified": "2025-12-08T12:41:21.324Z"}, {"entity": "publication", "iuid": "f9ddf419c2544b17840de75ae2763a2b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f9ddf419c2544b17840de75ae2763a2b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f9ddf419c2544b17840de75ae2763a2b"}}, "title": "Novel Synonymous and Deep Intronic Variants Causing Primary and Secondary Pyruvate Dehydrogenase Complex Deficiency.", "authors": [{"family": "Bruhn", "given": "Helene", "initials": "H", "orcid": "0009-0007-4449-5382", "researcher": {"href": "https://publications.scilifelab.se/researcher/789656ba85444c398bd2ebc03283f992.json"}}, {"family": "Naess", "given": "Karin", "initials": "K", "orcid": "0000-0003-4310-7927", "researcher": {"href": "https://publications.scilifelab.se/researcher/1cf2472011ec46bf841260c7515fbbfc.json"}}, {"family": "Ygberg", "given": "Sofia", "initials": "S", "orcid": "0000-0002-3854-2716", "researcher": {"href": "https://publications.scilifelab.se/researcher/ea34ee1594994492bc7dd8047503bbf0.json"}}, {"family": "Pe\u00f1a-P\u00e9rez", "given": "Luc\u00eda", "initials": "L", "orcid": "0000-0002-5044-7754", "researcher": {"href": "https://publications.scilifelab.se/researcher/111f8a8c4c6d4d2ea60e5fc76831b7fa.json"}}, {"family": "Lesko", "given": "Nicole", "initials": "N", "orcid": "0000-0001-8770-1878", "researcher": {"href": "https://publications.scilifelab.se/researcher/59b2ed29329e449bbe832174668d1d82.json"}}, {"family": "Wibom", "given": "Rolf", "initials": "R", "orcid": "0000-0001-6721-4642", "researcher": {"href": "https://publications.scilifelab.se/researcher/c7d5fc666ef84a8784d8b28ecf233146.json"}}, {"family": "Freyer", "given": "Christoph", "initials": "C", "orcid": "0000-0003-0418-1673", "researcher": {"href": "https://publications.scilifelab.se/researcher/888298d25fb94acca7639063d3592373.json"}}, {"family": "Stranneheim", "given": "Henrik", "initials": "H", "orcid": "0009-0009-1335-8021", "researcher": {"href": "https://publications.scilifelab.se/researcher/8dc7b1a3b5964ffca53a16c13a01d7ab.json"}}, {"family": "Wedell", "given": "Anna", "initials": "A", "orcid": "0000-0002-2612-6301", "researcher": {"href": "https://publications.scilifelab.se/researcher/15f660ec95994b6a83d540e48c9b7610.json"}}, {"family": "Wredenberg", "given": "Anna", "initials": "A", "orcid": "0000-0002-2500-6121", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ea9ee7305424cdb8c238ef569e5be03.json"}}], "type": "journal article", "published": "2024-03-25", "journal": {"title": "Hum. Mutat.", "issn": "1098-1004", "volume": "2024", "pages": "1611838", "issn-l": "1059-7794"}, "abstract": "Pyruvate dehydrogenase complex deficiency (PDCD) is a defect of aerobic carbohydrate metabolism that causes neurological disorders with varying degrees of severity. We report the clinical, biochemical, and molecular findings in patients with primary and secondary PDCD caused by novel atypical genetic variants. Whole-genome sequencing (WGS) identified the synonymous variants c.447A>G, p.(Lys149=) and c.570C>T, p.(Cys190=) in pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1), the deep intronic variants c.1023+2267G>A and c.1023+2302A>G in pyruvate dehydrogenase complex component X (PDHX), and c.185+15054G>A in thiamine pyrophosphokinase (TPK1). Analysis by Sanger and RNA sequencing of cDNA from patient blood and/or cultured fibroblasts showed that the synonymous variants in PDHA1 lead to aberrant splicing and skipping of exons 5 and 5-6 in one of the patients and transcripts lacking exon 6 in the other. The deep intronic variants in PDHX and TPK1 lead to insertion of intronic sequence in the corresponding transcripts. The splice defects in PDHA1 were more pronounced in cultured fibroblasts than in blood. Our findings expand the spectrum of pathogenic variants causing PDCD and highlight the importance of atypical variants leading to aberrant splicing. The severity of the splice defects and resulting biochemical dysfunction varied between tissues, stressing the importance of performing biochemical and transcript analysis in affected tissues. The two males with hemizygous synonymous PDHA1 variants have a mild phenotype and higher PDH enzyme activity than expected, which is consistent with aberrant but leaky splicing with a proportion of the transcripts remaining correctly spliced.", "doi": "10.1155/2024/1611838", "pmid": "40225937", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11919216"}], "notes": [], "created": "2024-11-21T10:09:24.804Z", "modified": "2025-12-04T19:36:40.885Z"}, {"entity": "publication", "iuid": "94cdf9ed17a340d9a18e9348cf2fb025", "links": {"self": {"href": "https://publications.scilifelab.se/publication/94cdf9ed17a340d9a18e9348cf2fb025.json"}, "display": {"href": "https://publications.scilifelab.se/publication/94cdf9ed17a340d9a18e9348cf2fb025"}}, "title": "Severe congenital lactic acidosis and hypertrophic cardiomyopathy caused by an intronic variant in NDUFB7.", "authors": [{"family": "Correia", "given": "Sandrina P", "initials": "SP"}, {"family": "Moedas", "given": "Marco F", "initials": "MF"}, {"family": "Naess", "given": "Karin", "initials": "K"}, {"family": "Bruhn", "given": "Helene", "initials": "H"}, {"family": "Maffezzini", "given": "Camilla", "initials": "C"}, {"family": "Calvo-Garrido", "given": "Javier", "initials": "J"}, {"family": "Lesko", "given": "Nicole", "initials": "N"}, {"family": "Wibom", "given": "Rolf", "initials": "R"}, {"family": "Schober", "given": "Florian A", "initials": "FA", "orcid": "0000-0003-4604-6170", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e9cd9d0742d40e3b5dc1abfde64d5c4.json"}}, {"family": "Jemt", "given": "Anders", "initials": "A"}, {"family": "Stranneheim", "given": "Henrik", "initials": "H"}, {"family": "Freyer", "given": "Christoph", "initials": "C", "orcid": "0000-0003-0418-1673", "researcher": {"href": "https://publications.scilifelab.se/researcher/888298d25fb94acca7639063d3592373.json"}}, {"family": "Wedell", "given": "Anna", "initials": "A"}, {"family": "Wredenberg", "given": "Anna", "initials": "A", "orcid": "0000-0002-2500-6121", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ea9ee7305424cdb8c238ef569e5be03.json"}}], "type": "journal article", "published": "2021-04-00", "journal": {"title": "Hum. Mutat.", "issn": "1098-1004", "volume": "42", "issue": "4", "pages": "378-384", "issn-l": "1059-7794"}, "abstract": "Mutations in structural subunits and assembly factors of complex I of the oxidative phosphorylation system constitute the most common cause of mitochondrial respiratory chain defects. Such mutations can present a wide range of clinical manifestations, varying from mild deficiencies to severe, lethal disorders. We describe a patient presenting intrauterine growth restriction and anemia, which displayed postpartum hypertrophic cardiomyopathy, lactic acidosis, encephalopathy, and a severe complex I defect with fatal outcome. Whole genome sequencing revealed an intronic biallelic mutation in the NDUFB7 gene (c.113-10C>G) and splicing pattern alterations in NDUFB7 messenger RNA were confirmed by RNA Sequencing. The detected variant resulted in a significant reduction of the NDUFB7 protein and reduced complex I activity. Complementation studies with expression of wild-type NDUFB7 in patient fibroblasts normalized complex I function. Here we report a case with a primary complex I defect due to a homozygous mutation in an intron region of the NDUFB7 gene.", "doi": "10.1002/humu.24173", "pmid": "33502047", "labels": {"Clinical Genomics Stockholm": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Clinical Genomics": "Service"}, "xrefs": [], "notes": [], "created": "2021-02-04T14:33:05.943Z", "modified": "2021-12-06T13:45:27.325Z"}, {"entity": "publication", "iuid": "131283b276484c18b504aa4dc0115f19", "links": {"self": {"href": "https://publications.scilifelab.se/publication/131283b276484c18b504aa4dc0115f19.json"}, "display": {"href": "https://publications.scilifelab.se/publication/131283b276484c18b504aa4dc0115f19"}}, "title": "The one-carbon pool controls mitochondrial energy metabolism via complex I and iron-sulfur clusters.", "authors": [{"family": "Schober", "given": "Florian A", "initials": "FA", "orcid": "0000-0003-4604-6170", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e9cd9d0742d40e3b5dc1abfde64d5c4.json"}}, {"family": "Moore", "given": "David", "initials": "D"}, {"family": "Atanassov", "given": "Ilian", "initials": "I", "orcid": "0000-0001-8259-2545", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8d22eab41e44364be8966abaf693de1.json"}}, {"family": "Moedas", "given": "Marco F", "initials": "MF", "orcid": "0000-0001-5461-0320", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a9cd9caaa014f4280544a243520e18c.json"}}, {"family": "Clemente", "given": "Paula", "initials": "P"}, {"family": "V\u00e9gv\u00e1ri", "given": "\u00c1kos", "initials": "\u00c1", "orcid": "0000-0002-1287-0906", "researcher": {"href": "https://publications.scilifelab.se/researcher/74be6e7c877e4f0da6c7ed3747f3ef9d.json"}}, {"family": "Fissi", "given": "Najla El", "initials": "NE", "orcid": "0000-0002-6631-4630", "researcher": {"href": "https://publications.scilifelab.se/researcher/dec87cba920947028856aadb5892f7a6.json"}}, {"family": "Filograna", "given": "Roberta", "initials": "R"}, {"family": "Bucher", "given": "Anna-Lena", "initials": "AL", "orcid": "0000-0002-9391-4850", "researcher": {"href": "https://publications.scilifelab.se/researcher/7ec4467fb36b44f0a0b1dfa056ec964d.json"}}, {"family": "Hinze", "given": "Yvonne", "initials": "Y", "orcid": "0000-0002-2966-9862", "researcher": {"href": "https://publications.scilifelab.se/researcher/a922a71f2fde43908945980353ed595a.json"}}, {"family": "The", "given": "Matthew", "initials": "M", "orcid": "0000-0002-5401-5553", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e90cde879dc41eaade439bcf951a646.json"}}, {"family": "Hedman", "given": "Erik", "initials": "E", "orcid": "0000-0003-4017-9749", "researcher": {"href": "https://publications.scilifelab.se/researcher/ffc752d50a6649248c6809ea5aec803d.json"}}, {"family": "Chernogubova", "given": "Ekaterina", "initials": "E"}, {"family": "Begzati", "given": "Arjana", "initials": "A", "orcid": "0000-0002-8770-8022", "researcher": {"href": "https://publications.scilifelab.se/researcher/a15af0dbd68445538bd92c89f6d901df.json"}}, {"family": "Wibom", "given": "Rolf", "initials": "R", "orcid": "0000-0001-6721-4642", "researcher": {"href": "https://publications.scilifelab.se/researcher/c7d5fc666ef84a8784d8b28ecf233146.json"}}, {"family": "Jain", "given": "Mohit", "initials": "M"}, {"family": "Nilsson", "given": "Roland", "initials": "R", "orcid": "0000-0002-6020-7498", "researcher": {"href": "https://publications.scilifelab.se/researcher/0667c6d082934d818445fe0187dbb23e.json"}}, {"family": "K\u00e4ll", "given": "Lukas", "initials": "L", "orcid": "0000-0001-5689-9797", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c9f4444f83e43d79c4772a430ca3969.json"}}, {"family": "Wedell", "given": "Anna", "initials": "A"}, {"family": "Freyer", "given": "Christoph", "initials": "C", "orcid": "0000-0003-0418-1673", "researcher": {"href": "https://publications.scilifelab.se/researcher/888298d25fb94acca7639063d3592373.json"}}, {"family": "Wredenberg", "given": "Anna", "initials": "A", "orcid": "0000-0002-2500-6121", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ea9ee7305424cdb8c238ef569e5be03.json"}}], "type": "journal article", "published": "2021-02-00", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "7", "issue": "8", "issn-l": "2375-2548"}, "abstract": "Induction of the one-carbon cycle is an early hallmark of mitochondrial dysfunction and cancer metabolism. Vital intermediary steps are localized to mitochondria, but it remains unclear how one-carbon availability connects to mitochondrial function. Here, we show that the one-carbon metabolite and methyl group donor S-adenosylmethionine (SAM) is pivotal for energy metabolism. A gradual decline in mitochondrial SAM (mitoSAM) causes hierarchical defects in fly and mouse, comprising loss of mitoSAM-dependent metabolites and impaired assembly of the oxidative phosphorylation system. Complex I stability and iron-sulfur cluster biosynthesis are directly controlled by mitoSAM levels, while other protein targets are predominantly methylated outside of the organelle before import. The mitoSAM pool follows its cytosolic production, establishing mitochondria as responsive receivers of one-carbon units. Thus, we demonstrate that cellular methylation potential is required for energy metabolism, with direct relevance for pathophysiology, aging, and cancer.", "doi": "10.1126/sciadv.abf0717", "pmid": "33608280", "labels": {"NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "7/8/eabf0717"}, {"db": "pmc", "key": "PMC7895438"}], "notes": [], "created": "2021-12-06T13:45:25.780Z", "modified": "2024-01-16T13:48:40.799Z"}]}