{"entity": "researcher", "timestamp": "2026-09-23T19:14:06.569Z", "family": "Filograna", "given": "Roberta", "initials": "R", "orcid": "0000-0002-6581-9426", "affiliations": ["Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/4cf8dcfdeeeb418b81b5e9301fe5efe8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/4cf8dcfdeeeb418b81b5e9301fe5efe8"}}, "publications": [{"entity": "publication", "iuid": "29a38c45c2fb4b89a7324bb57a0a6437", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/29a38c45c2fb4b89a7324bb57a0a6437.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/29a38c45c2fb4b89a7324bb57a0a6437"}}, "title": "The CHCHD2-CHCHD10 protein complex is modulated by mitochondrial dysfunction and alters lipid homeostasis in the mouse brain.", "authors": [{"family": "Gerlach", "given": "Jule", "initials": "J"}, {"family": "Pireddu", "given": "Paola", "initials": "P"}, {"family": "Zhang", "given": "Xiaoqun", "initials": "X"}, {"family": "Wetzel", "given": "Simon", "initials": "S", "orcid": "0000-0003-1831-0376", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8a28f25f4b494330b26a840ecb92ca43.json"}}, {"family": "Mennuni", "given": "Mara", "initials": "M"}, {"family": "Milenkovic", "given": "Dusanka", "initials": "D"}, {"family": "Nolte", "given": "Hendrik", "initials": "H"}, {"family": "da Silva Rodrigues", "given": "Fernanda", "initials": "F"}, {"family": "Branzell", "given": "Niclas", "initials": "N", "orcid": "0009-0009-3472-6903", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e9c07f5b2d4e4a7d99522bfe7342abc2.json"}}, {"family": "Kaya", "given": "Ibrahim", "initials": "I", "orcid": "0000-0003-3345-5602", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/43885795cb254e2cba6fe8b538fbfaef.json"}}, {"family": "Villegas", "given": "Rodolfo Garcia", "initials": "RG"}, {"family": "Rubalcava-Gracia", "given": "Diana", "initials": "D"}, {"family": "Alsina", "given": "David", "initials": "D"}, {"family": "Feederle", "given": "Regina", "initials": "R", "orcid": "0000-0002-3981-367X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/56117592359d4707ade25b434c0a620e.json"}}, {"family": "Andr\u00e9n", "given": "Per E", "initials": "PE", "orcid": "0000-0002-4062-7743", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f1dd27e8b238475383983480e10099f6.json"}}, {"family": "Langer", "given": "Thomas", "initials": "T"}, {"family": "Svenningsson", "given": "Per", "initials": "P"}, {"family": "Filograna", "given": "Roberta", "initials": "R", "orcid": "0000-0002-6581-9426", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4cf8dcfdeeeb418b81b5e9301fe5efe8.json"}}], "type": "journal article", "published": "2025-10-06", "journal": {"title": "Cell Death Dis", "issn": "2041-4889", "volume": "16", "issue": "1", "pages": "693", "issn-l": "2041-4889"}, "abstract": "The highly conserved CHCHD2 and CHCHD10 are small mitochondrial proteins residing in the intermembrane space. Recently, mutations in the genes encoding these proteins have been linked to severe disorders, including Parkinson's disease and amyotrophic lateral sclerosis. In cultured cells, a small fraction of CHCHD2 and CHCHD10 oligomerize to form a high molecular weight complex of unknown function. Here, we generated a whole-body Chchd2 knockout mouse to investigate the in vivo role of CHCHD2 and its protein complex. We show that CHCHD2 is crucial for sustaining full motor capacity, normal striatal dopamine levels, and lipid homeostasis in the brain of adult male mice. We also demonstrate that in mouse tissues, CHCHD2 and CHCHD10 exist exclusively as a high molecular weight complex, whose levels are finely tuned under physiological conditions. In response to mitochondrial dysfunction, the abundance and size of the CHCHD2-CHCHD10 complex increase, a mechanism conserved across different tissues. Although the loss of CHCHD2 does not abolish CHCHD10 oligomerization, it enhances cell vulnerability to mitochondrial stress, suggesting that CHCHD2 is protective against mitochondrial damage. Our findings uncover the role of CHCHD2 in preserving tissue homeostasis and provide important insights into the involvement of the CHCHD2-CHCHD10 complex in human diseases.", "doi": "10.1038/s41419-025-08030-z", "pmid": "41053020", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12501252"}, {"db": "pii", "key": "10.1038/s41419-025-08030-z"}], "notes": [], "created": "2026-09-23T11:37:18.831Z", "modified": "2026-09-23T11:37:19.026Z"}, {"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": "b0b132e58d9c4d669cf7f59bdf99bb17", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b0b132e58d9c4d669cf7f59bdf99bb17.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b0b132e58d9c4d669cf7f59bdf99bb17"}}, "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"}, {"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"}, {"family": "Koolmeister", "given": "Camilla", "initials": "C"}, {"family": "Wibom", "given": "Rolf", "initials": "R"}, {"family": "Riggare", "given": "Sara", "initials": "S"}, {"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"}, {"family": "Larsson", "given": "Nils G\u00f6ran", "initials": "NG"}], "type": "posted-content", "published": "2023-09-02", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2023.09.02.556020", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-09-23T14:27:29.824Z", "modified": "2026-09-23T14:27:29.876Z"}, {"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"}]}