{"entity": "researcher", "timestamp": "2026-07-20T12:59:34.419Z", "family": "Mennuni", "given": "Mara", "initials": "M", "orcid": "0000-0001-6199-6233", "affiliations": ["Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/0d3b8d76aacd4f47ae62d0de66e9222a.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/0d3b8d76aacd4f47ae62d0de66e9222a"}}, "publications": [{"entity": "publication", "iuid": "2e917c797feb476e8c34b4c4e6e2a631", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2e917c797feb476e8c34b4c4e6e2a631.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2e917c797feb476e8c34b4c4e6e2a631"}}, "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.scilifelab.se/researcher/ddd21b38f82f4624a40679559339c845.json"}}, {"family": "Mennuni", "given": "Mara", "initials": "M", "orcid": "0000-0001-6199-6233", "researcher": {"href": "https://publications.scilifelab.se/researcher/0d3b8d76aacd4f47ae62d0de66e9222a.json"}}, {"family": "Milenkovic", "given": "Dusanka", "initials": "D", "orcid": "0000-0003-0151-8760", "researcher": {"href": "https://publications.scilifelab.se/researcher/7667a08efad244b88892a772f51ccf50.json"}}, {"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.scilifelab.se/researcher/4bde4ad10f0146379233871ea29ea918.json"}}, {"family": "Kaya", "given": "Ibrahim", "initials": "I", "orcid": "0000-0003-3345-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/99a00a900df8419f96fafa97344e56ea.json"}}, {"family": "Villegas", "given": "Rodolfo Garcia", "initials": "RG"}, {"family": "Rubalcava-Gracia", "given": "Diana", "initials": "D", "orcid": "0000-0002-4615-7375", "researcher": {"href": "https://publications.scilifelab.se/researcher/99b075c43c2244ee9a26fae7b09d523a.json"}}, {"family": "Alsina", "given": "David", "initials": "D"}, {"family": "Feederle", "given": "Regina", "initials": "R", "orcid": "0000-0002-3981-367X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c19111a0c7af42d4a22b7221e4426909.json"}}, {"family": "Andr\u00e9n", "given": "Per E", "initials": "PE", "orcid": "0000-0002-4062-7743", "researcher": {"href": "https://publications.scilifelab.se/researcher/64f6381de42949db8d30b56b526f3e26.json"}}, {"family": "Langer", "given": "Thomas", "initials": "T"}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}}, {"family": "Filograna", "given": "Roberta", "initials": "R", "orcid": "0000-0002-6581-9426", "researcher": {"href": "https://publications.scilifelab.se/researcher/7d215cffe2dc48a18d051a2229c8ce9f.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": {"Spatial Mass Spectrometry": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC12501252"}, {"db": "pii", "key": "10.1038/s41419-025-08030-z"}], "notes": [], "created": "2025-11-21T09:46:18.171Z", "modified": "2025-11-27T13:31:05.879Z"}, {"entity": "publication", "iuid": "a8f05f12d3914490af074ff93cd54013", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a8f05f12d3914490af074ff93cd54013.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a8f05f12d3914490af074ff93cd54013"}}, "title": "Metabolic resistance to the inhibition of mitochondrial transcription revealed by CRISPR-Cas9 screen.", "authors": [{"family": "Mennuni", "given": "Mara", "initials": "M", "orcid": "0000-0001-6199-6233", "researcher": {"href": "https://publications.scilifelab.se/researcher/0d3b8d76aacd4f47ae62d0de66e9222a.json"}}, {"family": "Filograna", "given": "Roberta", "initials": "R", "orcid": "0000-0002-6581-9426", "researcher": {"href": "https://publications.scilifelab.se/researcher/7d215cffe2dc48a18d051a2229c8ce9f.json"}}, {"family": "Felser", "given": "Andrea", "initials": "A"}, {"family": "Bonekamp", "given": "Nina A", "initials": "NA", "orcid": "0000-0001-9748-8089", "researcher": {"href": "https://publications.scilifelab.se/researcher/786f4a3ca29a4033b3252e014e6785df.json"}}, {"family": "Giavalisco", "given": "Patrick", "initials": "P", "orcid": "0000-0002-4636-1827", "researcher": {"href": "https://publications.scilifelab.se/researcher/d8b3ada5024b4a23a32cdc392f92fb81.json"}}, {"family": "Lytovchenko", "given": "Oleksandr", "initials": "O", "orcid": "0000-0003-1032-2612", "researcher": {"href": "https://publications.scilifelab.se/researcher/3fb9454d524a470196c06792d4b47a7c.json"}}, {"family": "Larsson", "given": "Nils-G\u00f6ran", "initials": "N"}], "type": "journal article", "published": "2022-01-05", "journal": {"title": "EMBO Rep.", "issn": "1469-3178", "issn-l": "1469-221X", "volume": "23", "issue": "1", "pages": "e53054"}, "abstract": "Cancer cells depend on mitochondria to sustain their increased metabolic need and mitochondria therefore constitute possible targets for cancer treatment. We recently developed small-molecule inhibitors of mitochondrial transcription (IMTs) that selectively impair mitochondrial gene expression. IMTs have potent antitumor properties in vitro and in vivo, without affecting normal tissues. Because therapy-induced resistance is a major constraint to successful cancer therapy, we investigated mechanisms conferring resistance to IMTs. We employed a CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats)-(CRISP-associated protein 9) whole-genome screen to determine pathways conferring resistance to acute IMT1 treatment. Loss of genes belonging to von Hippel-Lindau (VHL) and mammalian target of rapamycin complex 1 (mTORC1) pathways caused resistance to acute IMT1 treatment and the relevance of these pathways was confirmed by chemical modulation. We also generated cells resistant to chronic IMT treatment to understand responses to persistent mitochondrial gene expression impairment. We report that IMT1-acquired resistance occurs through a compensatory increase of mitochondrial DNA (mtDNA) expression and cellular metabolites. We found that mitochondrial transcription factor A (TFAM) downregulation and inhibition of mitochondrial translation impaired survival of resistant cells. The identified susceptibility and resistance mechanisms to IMTs may be relevant for different types of mitochondria-targeted therapies.", "doi": "10.15252/embr.202153054", "pmid": "34779571", "labels": {"CRISPR Functional Genomics": "Service", "NGI Short read": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8728608"}], "notes": [], "created": "2022-06-20T12:50:08.214Z", "modified": "2022-08-19T09:49:54.313Z"}, {"entity": "publication", "iuid": "4f5ab34ce2334c658b9c8fb041665f50", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4f5ab34ce2334c658b9c8fb041665f50.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4f5ab34ce2334c658b9c8fb041665f50"}}, "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.scilifelab.se/researcher/7d215cffe2dc48a18d051a2229c8ce9f.json"}}, {"family": "Lee", "given": "Seungmin", "initials": "S", "orcid": "0000-0002-0903-0973", "researcher": {"href": "https://publications.scilifelab.se/researcher/175203731b3048bc8763ab5155e6b84f.json"}}, {"family": "Tiklov\u00e1", "given": "Katar\u00edna", "initials": "K"}, {"family": "Mennuni", "given": "Mara", "initials": "M", "orcid": "0000-0001-6199-6233", "researcher": {"href": "https://publications.scilifelab.se/researcher/0d3b8d76aacd4f47ae62d0de66e9222a.json"}}, {"family": "Jonsson", "given": "Viktor", "initials": "V", "orcid": "0000-0002-1445-5220", "researcher": {"href": "https://publications.scilifelab.se/researcher/a1ed4977f0c243ad847c4ec0ab24fd88.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.scilifelab.se/researcher/49eae62ecbbf45848dc5d2808d363010.json"}}, {"family": "Shupliakov", "given": "Oleg", "initials": "O", "orcid": "0000-0001-5352-6848", "researcher": {"href": "https://publications.scilifelab.se/researcher/136d6cd739f04017accb6198a9626a38.json"}}, {"family": "Koolmeister", "given": "Camilla", "initials": "C", "orcid": "0000-0002-4052-3442", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a59865b375744c7adeeaed402a2e0b5.json"}}, {"family": "Olson", "given": "Lars", "initials": "L", "orcid": "0000-0001-7378-7420", "researcher": {"href": "https://publications.scilifelab.se/researcher/80e5c20645b94c0b94f2405e7ae3e8e2.json"}}, {"family": "Perlmann", "given": "Thomas", "initials": "T"}, {"family": "Larsson", "given": "Nils-G\u00f6ran", "initials": "NG", "orcid": "0000-0001-5100-996X", "researcher": {"href": "https://publications.scilifelab.se/researcher/1dc68aa2893a4ab8845fc32d8d6bc59a.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": {"Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC8496783"}, {"db": "pii", "key": "PGENETICS-D-21-00764"}], "notes": [], "created": "2023-03-03T21:44:47.290Z", "modified": "2023-03-03T21:44:47.441Z"}]}