{"entity": "researcher", "timestamp": "2026-07-13T08:55:20.731Z", "family": "Singh", "given": "Vivek", "initials": "V", "orcid": "0000-0003-4656-3362", "affiliations": ["Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Solna, Sweden", "Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden"], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/0576b8ffc93d42f6b47d9d0d7d01bbd0.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/0576b8ffc93d42f6b47d9d0d7d01bbd0"}}, "publications": [{"entity": "publication", "iuid": "c586da7cc0cf4911a6d5d9d9ce6be426", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c586da7cc0cf4911a6d5d9d9ce6be426.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c586da7cc0cf4911a6d5d9d9ce6be426"}}, "title": "Structural basis for late maturation steps of mitochondrial respiratory chain complex IV within the human respirasome.", "authors": [{"family": "Nguyen", "given": "Minh Duc", "initials": "MD", "orcid": "0000-0003-2945-9707", "researcher": {"href": "https://publications.scilifelab.se/researcher/c66f3b3aa7c147558c0c1a7a1b079d09.json"}}, {"family": "Sierra-Magro", "given": "Ana", "initials": "A", "orcid": "0000-0002-2810-8377", "researcher": {"href": "https://publications.scilifelab.se/researcher/eae822e08d3443fd9d7addb3616553c5.json"}}, {"family": "Singh", "given": "Vivek", "initials": "V", "orcid": "0000-0003-4656-3362", "researcher": {"href": "https://publications.scilifelab.se/researcher/0576b8ffc93d42f6b47d9d0d7d01bbd0.json"}}, {"family": "Khawaja", "given": "Anas", "initials": "A", "orcid": "0000-0002-9721-7454", "researcher": {"href": "https://publications.scilifelab.se/researcher/a699763ef41f49d6b558e208fedc3db8.json"}}, {"family": "Tim\u00f3n-G\u00f3mez", "given": "Alba", "initials": "A", "orcid": "0000-0001-9811-8557", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1bd3e28e3214dd58dc5eddc21d469b3.json"}}, {"family": "Barrientos", "given": "Antoni", "initials": "A", "orcid": "0000-0001-9018-3231", "researcher": {"href": "https://publications.scilifelab.se/researcher/07a9331fc2df454c9c6e288f70c8c976.json"}}, {"family": "Rorbach", "given": "Joanna", "initials": "J", "orcid": "0000-0002-2891-2840", "researcher": {"href": "https://publications.scilifelab.se/researcher/a069374613a7403b818ce7ca400f3627.json"}}], "type": "journal article", "published": "2026-01-10", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723"}, "abstract": "The mitochondrial respiratory chain comprises four multimeric complexes (CI-CIV) that drive oxidative phosphorylation by transferring electrons to oxygen and generating the proton gradient required for ATP synthesis. These complexes can associate into supercomplexes (SCs), such as the CI + CIII\u2082 + CIV respirasome, but how SCs form, by joining preassembled complexes or by engaging partially assembled intermediates, remains unresolved. Here, we use cryo-electron microscopy to determine high-resolution structures of native human CI + CIII\u2082 + CIV late-assembly intermediates. Together with biochemical analyses, these structures show that respirasome biogenesis concludes with the final maturation of CIV while it is associated with fully assembled CI and CIII\u2082. We identify HIGD2A as a placeholder factor within isolated and supercomplexed CIV that is replaced by subunit NDUFA4 during the last step of CIV and respirasome assembly. This mechanism suggests that placeholders such as HIGD2A act as molecular timers, preventing premature incorporation of NDUFA4 or its isoforms and ensuring the orderly progression of pre-SC particles into functional respirasomes. Since defects in CIV assembly, including NDUFA4 deficiencies, cause severe encephalomyopathies and neurodegenerative disorders, understanding the molecular architecture and assembly pathways of isolated and supercomplexed CIV offers insight into the pathogenic mechanisms underlying these conditions.", "doi": "10.1038/s41467-025-68274-3", "pmid": "41519940", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-025-68274-3"}], "notes": [], "created": "2026-01-25T10:08:32.804Z", "modified": "2026-01-25T10:08:33.699Z"}, {"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": "62278042bce741a7830004b9bee7a21c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/62278042bce741a7830004b9bee7a21c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/62278042bce741a7830004b9bee7a21c"}}, "title": "Structural basis of mitochondrial translation", "authors": [{"family": "Aibara", "given": "Shintaro", "initials": "S", "orcid": "0000-0003-2221-482X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d66746c4bec5414da78b2a325a13328f.json"}}, {"family": "Singh", "given": "Vivek", "initials": "V", "orcid": "0000-0003-4656-3362", "researcher": {"href": "https://publications.scilifelab.se/researcher/0576b8ffc93d42f6b47d9d0d7d01bbd0.json"}}, {"family": "Modelska", "given": "Angelika", "initials": "A"}, {"family": "Amunts", "given": "Alexey", "initials": "A", "orcid": "0000-0002-5302-1740", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7d0bf36ad1a47f5b5b88f78d1e15395.json"}}], "type": "journal-article", "published": "2020-08-19", "journal": {"volume": "9", "issn": "2050-084X", "issue": null, "pages": "1-17", "title": "Elife", "issn-l": "2050-084X"}, "abstract": "Translation of mitochondrial messenger RNA (mt-mRNA) is performed by distinct mitoribosomes comprising at least 36 mitochondria-specific proteins. How these mitoribosomal proteins assist in the binding of mt-mRNA and to what extent they are involved in the translocation of transfer RNA (mt-tRNA) is unclear. To visualize the process of translation in human mitochondria, we report ~3.0 \u00c5 resolution structure of the human mitoribosome, including the L7/L12 stalk, and eight structures of its functional complexes with mt-mRNA, mt-tRNAs, recycling factor and additional trans factors. The study reveals a transacting protein module LRPPRC-SLIRP that delivers mt-mRNA to the mitoribosomal small subunit through a dedicated platform formed by the mitochondria-specific protein mS39. Mitoribosomal proteins of the large subunit mL40, mL48, and mL64 coordinate translocation of mt-tRNA. The comparison between those structures shows dynamic interactions between the mitoribosome and its ligands, suggesting a sequential mechanism of conformational changes.", "doi": "10.7554/elife.58362", "pmid": "32812867", "labels": {"Cryo-EM": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7438116"}, {"db": "pii", "key": "58362"}], "notes": [], "created": "2020-08-19T17:38:17.731Z", "modified": "2023-06-19T08:55:09.334Z"}]}