{"entity": "researcher", "timestamp": "2026-09-23T19:14:54.081Z", "family": "Larsson", "given": "Nils-G\u00f6ran", "initials": "NG", "orcid": "0000-0001-5100-996X", "affiliations": ["Division of Molecular Metabolism, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/a457478920e048b59b225f2561d3e07a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/a457478920e048b59b225f2561d3e07a"}}, "publications": [{"entity": "publication", "iuid": "13ecf5a6bdbd480c993fe7cff54f2c25", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/13ecf5a6bdbd480c993fe7cff54f2c25.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/13ecf5a6bdbd480c993fe7cff54f2c25"}}, "title": "LRPPRC and SLIRP synergize to maintain sufficient and orderly mammalian mitochondrial translation.", "authors": [{"family": "Rubalcava-Gracia", "given": "Diana", "initials": "D", "orcid": "0000-0002-4615-7375", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cdb2286b21364ad795f691aad005a4e1.json"}}, {"family": "Bubb", "given": "Kristina", "initials": "K"}, {"family": "Levander", "given": "Fredrik", "initials": "F", "orcid": "0000-0002-0710-9792", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d3aaa3dcdb4f4e9f9b4bd44097d85d0c.json"}}, {"family": "Burr", "given": "Stephen P", "initials": "SP"}, {"family": "August", "given": "Amelie V", "initials": "AV"}, {"family": "Chinnery", "given": "Patrick F", "initials": "PF"}, {"family": "Koolmeister", "given": "Camilla", "initials": "C"}, {"family": "Larsson", "given": "Nils-G\u00f6ran", "initials": "NG", "orcid": "0000-0001-5100-996X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a457478920e048b59b225f2561d3e07a.json"}}], "type": "journal article", "published": "2024-10-14", "journal": {"title": "Nucleic Acids Res.", "issn": "1362-4962", "volume": "52", "issue": "18", "pages": "11266-11282", "issn-l": "0305-1048"}, "abstract": "In mammals, the leucine-rich pentatricopeptide repeat protein (LRPPRC) and the stem-loop interacting RNA-binding protein (SLIRP) form a complex in the mitochondrial matrix that is required throughout the life cycle of most mitochondrial mRNAs. Although pathogenic mutations in the LRPPRC and SLIRP genes cause devastating human mitochondrial diseases, the in vivo function of the corresponding proteins is incompletely understood. We show here that loss of SLIRP in mice causes a decrease of complex I levels whereas other OXPHOS complexes are unaffected. We generated knock-in mice to study the in vivo interdependency of SLIRP and LRPPRC by mutating specific amino acids necessary for protein complex formation. When protein complex formation is disrupted, LRPPRC is partially degraded and SLIRP disappears. Livers from Lrpprc knock-in mice had impaired mitochondrial translation except for a marked increase in the synthesis of ATP8. Furthermore, the introduction of a heteroplasmic pathogenic mtDNA mutation (m.C5024T of the tRNAAla gene) into Slirp knockout mice causes an additive effect on mitochondrial translation leading to embryonic lethality and reduced growth of mouse embryonic fibroblasts. To summarize, we report that the LRPPRC/SLIRP protein complex is critical for maintaining normal complex I levels and that it also coordinates mitochondrial translation in a tissue-specific manner.", "doi": "10.1093/nar/gkae662", "pmid": "39087558", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11472161"}, {"db": "pii", "key": "7725477"}], "notes": [], "created": "2026-09-23T09:08:01.732Z", "modified": "2026-09-23T09:08:01.908Z"}, {"entity": "publication", "iuid": "8018a317711a471b98c41ee1578a5c83", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8018a317711a471b98c41ee1578a5c83.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8018a317711a471b98c41ee1578a5c83"}}, "title": "PARKIN is not required to sustain OXPHOS function in adult mammalian tissues.", "authors": [{"family": "Filograna", "given": "Roberta", "initials": "R", "orcid": "0000-0002-6581-9426", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4cf8dcfdeeeb418b81b5e9301fe5efe8.json"}}, {"family": "Gerlach", "given": "Jule", "initials": "J"}, {"family": "Choi", "given": "Hae-Na", "initials": "HN"}, {"family": "Rigoni", "given": "Giovanni", "initials": "G"}, {"family": "Barbaro", "given": "Michela", "initials": "M", "orcid": "0000-0002-7598-9330", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/537ef6d1505f497fa6d57c085e15e515.json"}}, {"family": "Oscarson", "given": "Mikael", "initials": "M"}, {"family": "Lee", "given": "Seungmin", "initials": "S"}, {"family": "Tiklova", "given": "Katarina", "initials": "K"}, {"family": "Ringn\u00e9r", "given": "Markus", "initials": "M", "orcid": "0000-0001-5469-8940", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/949fda08083846abae1c0ee20e6bceb1.json"}}, {"family": "Koolmeister", "given": "Camilla", "initials": "C"}, {"family": "Wibom", "given": "Rolf", "initials": "R"}, {"family": "Riggare", "given": "Sara", "initials": "S", "orcid": "0000-0002-2256-7310", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/df2606e844d34ef48cf24ce8a04c2503.json"}}, {"family": "Nennesmo", "given": "Inger", "initials": "I"}, {"family": "Perlmann", "given": "Thomas", "initials": "T"}, {"family": "Wredenberg", "given": "Anna", "initials": "A"}, {"family": "Wedell", "given": "Anna", "initials": "A"}, {"family": "Motori", "given": "Elisa", "initials": "E"}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b01bbacfa24e4b9794734bf1121d1c38.json"}}, {"family": "Larsson", "given": "Nils-G\u00f6ran", "initials": "NG", "orcid": "0000-0001-5100-996X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a457478920e048b59b225f2561d3e07a.json"}}], "type": "journal article", "published": "2024-04-29", "journal": {"title": "NPJ Parkinsons Dis", "issn": "2373-8057", "volume": "10", "issue": "1", "pages": "93", "issn-l": null}, "abstract": "Loss-of-function variants in the PRKN gene encoding the ubiquitin E3 ligase PARKIN cause autosomal recessive early-onset Parkinson's disease (PD). Extensive in vitro and in vivo studies have reported that PARKIN is involved in multiple pathways of mitochondrial quality control, including mitochondrial degradation and biogenesis. However, these findings are surrounded by substantial controversy due to conflicting experimental data. In addition, the existing PARKIN-deficient mouse models have failed to faithfully recapitulate PD phenotypes. Therefore, we have investigated the mitochondrial role of PARKIN during ageing and in response to stress by employing a series of conditional Parkin knockout mice. We report that PARKIN loss does not affect oxidative phosphorylation (OXPHOS) capacity and mitochondrial DNA (mtDNA) levels in the brain, heart, and skeletal muscle of aged mice. We also demonstrate that PARKIN deficiency does not exacerbate the brain defects and the pro-inflammatory phenotype observed in mice carrying high levels of mtDNA mutations. To rule out compensatory mechanisms activated during embryonic development of Parkin-deficient mice, we generated a mouse model where loss of PARKIN was induced in adult dopaminergic (DA) neurons. Surprisingly, also these mice did not show motor impairment or neurodegeneration, and no major transcriptional changes were found in isolated midbrain DA neurons. Finally, we report a patient with compound heterozygous PRKN pathogenic variants that lacks PARKIN and has developed PD. The PARKIN deficiency did not impair OXPHOS activities or induce mitochondrial pathology in skeletal muscle from the patient. Altogether, our results argue that PARKIN is dispensable for OXPHOS function in adult mammalian tissues.", "doi": "10.1038/s41531-024-00707-0", "pmid": "38684669", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11058849"}, {"db": "pii", "key": "10.1038/s41531-024-00707-0"}], "notes": [], "created": "2026-09-23T11:12:19.110Z", "modified": "2026-09-23T11:12:19.264Z"}, {"entity": "publication", "iuid": "faab66e081e74369bab9b78311eb90c2", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/faab66e081e74369bab9b78311eb90c2.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/faab66e081e74369bab9b78311eb90c2"}}, "title": "Mitochondrial dysfunction in adult midbrain dopamine neurons triggers an early immune response.", "authors": [{"family": "Filograna", "given": "Roberta", "initials": "R", "orcid": "0000-0002-6581-9426", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4cf8dcfdeeeb418b81b5e9301fe5efe8.json"}}, {"family": "Lee", "given": "Seungmin", "initials": "S", "orcid": "0000-0002-0903-0973", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d2cc3227ae68425090b0a5a836e9009e.json"}}, {"family": "Tiklov\u00e1", "given": "Katar\u00edna", "initials": "K"}, {"family": "Mennuni", "given": "Mara", "initials": "M", "orcid": "0000-0001-6199-6233", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cb0827ce281748f896183545feb27602.json"}}, {"family": "Jonsson", "given": "Viktor", "initials": "V", "orcid": "0000-0002-1445-5220", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8068fef596794494add13b3a4bc35768.json"}}, {"family": "Ringn\u00e9r", "given": "Markus", "initials": "M"}, {"family": "Gillberg", "given": "Linda", "initials": "L"}, {"family": "Sopova", "given": "Elena", "initials": "E", "orcid": "0000-0001-7561-331X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ff45a8ead3b440cba414cc1ec7775268.json"}}, {"family": "Shupliakov", "given": "Oleg", "initials": "O", "orcid": "0000-0001-5352-6848", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e7c2034256bf49d4a810b5df729703f6.json"}}, {"family": "Koolmeister", "given": "Camilla", "initials": "C", "orcid": "0000-0002-4052-3442", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fc4dd3f3c5074be8bec342ece37a15c5.json"}}, {"family": "Olson", "given": "Lars", "initials": "L", "orcid": "0000-0001-7378-7420", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e51b629d32a14303a80138346d53b827.json"}}, {"family": "Perlmann", "given": "Thomas", "initials": "T"}, {"family": "Larsson", "given": "Nils-G\u00f6ran", "initials": "NG", "orcid": "0000-0001-5100-996X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a457478920e048b59b225f2561d3e07a.json"}}], "type": "journal article", "published": "2021-09-00", "journal": {"title": "PLoS Genet", "issn": "1553-7404", "volume": "17", "issue": "9", "pages": "e1009822", "issn-l": "1553-7390"}, "abstract": "Dopamine (DA) neurons of the midbrain are at risk to become affected by mitochondrial damage over time and mitochondrial defects have been frequently reported in Parkinson's disease (PD) patients. However, the causal contribution of adult-onset mitochondrial dysfunction to PD remains uncertain. Here, we developed a mouse model lacking Mitofusin 2 (MFN2), a key regulator of mitochondrial network homeostasis, in adult midbrain DA neurons. The knockout mice develop severe and progressive DA neuron-specific mitochondrial dysfunction resulting in neurodegeneration and parkinsonism. To gain further insights into pathophysiological events, we performed transcriptomic analyses of isolated DA neurons and found that mitochondrial dysfunction triggers an early onset immune response, which precedes mitochondrial swelling, mtDNA depletion, respiratory chain deficiency and cell death. Our experiments show that the immune response is an early pathological event when mitochondrial dysfunction is induced in adult midbrain DA neurons and that neuronal death may be promoted non-cell autonomously by the cross-talk and activation of surrounding glial cells.", "doi": "10.1371/journal.pgen.1009822", "pmid": "34570766", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8496783"}, {"db": "pii", "key": "PGENETICS-D-21-00764"}], "notes": [], "created": "2026-09-23T11:05:38.667Z", "modified": "2026-09-23T11:05:39.024Z"}]}