{"entity": "researcher", "timestamp": "2026-08-20T20:40:58.846Z", "family": "Milletti", "given": "Giacomo", "initials": "G", "orcid": "0000-0003-2391-342X", "affiliations": ["DNA Replication and Cancer Group, Danish Cancer Institute, Copenhagen, Denmark."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/57f829170c13433d95819874b6fa3952.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/57f829170c13433d95819874b6fa3952"}}, "publications": [{"entity": "publication", "iuid": "5137acade2f14370b914614b3b1b44fa", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5137acade2f14370b914614b3b1b44fa.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5137acade2f14370b914614b3b1b44fa"}}, "title": "The PP2A-B55\u03b1 phosphatase is a master regulator of mitochondrial degradation and biogenesis.", "authors": [{"family": "Cianfanelli", "given": "Valentina", "initials": "V", "orcid": "0000-0002-3857-9463", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ecd317d35f4142febdd006e4c19ecd3b.json"}}, {"family": "Nanni", "given": "Monica", "initials": "M", "orcid": "0000-0001-5706-0053", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/09b0dc7e755640268eb404b8984fe701.json"}}, {"family": "Corr\u00e0", "given": "Samantha", "initials": "S", "orcid": "0000-0003-1985-6194", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/34aed5b4b7d14834bcbcd1550714f9ef.json"}}, {"family": "Mauri", "given": "Sofia", "initials": "S", "orcid": "0000-0003-3931-1490", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0e0ea3075fda4ba18327bc96a9123f69.json"}}, {"family": "Sumpton", "given": "David", "initials": "D", "orcid": "0000-0002-9004-4079", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7f3a17d1b74741f8bccfff7c0ad05b19.json"}}, {"family": "Lilla", "given": "Sergio", "initials": "S", "orcid": "0000-0003-3142-7640", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7a5956d3819947df8122ec1601025bbc.json"}}, {"family": "De Cegli", "given": "Rossella", "initials": "R", "orcid": "0000-0002-8526-8692", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1269d7def39540659533698e1282ce13.json"}}, {"family": "Bordi", "given": "Matteo", "initials": "M", "orcid": "0000-0001-8207-8546", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9c34176b2b1141f6a41d23f49de8e4ec.json"}}, {"family": "Milletti", "given": "Giacomo", "initials": "G", "orcid": "0000-0003-2391-342X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/57f829170c13433d95819874b6fa3952.json"}}, {"family": "Ferraina", "given": "Caterina", "initials": "C", "orcid": "0000-0002-3770-4437", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/eb9f5ebe210040f78d03e3bc8503c727.json"}}, {"family": "Hall", "given": "Arnaldur", "initials": "A", "orcid": "0000-0001-6847-4438", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f4c8a78056504735b11d15abd86dc46d.json"}}, {"family": "Petraroia", "given": "Michele", "initials": "M", "orcid": "0009-0000-0329-1155", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/10cc6330b16e4a338e87c3a38ccb36da.json"}}, {"family": "Clausi", "given": "Valentina", "initials": "V", "orcid": "0009-0008-2662-4774", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/027ce4a5d2f745b392ee0a6e92f65b5d.json"}}, {"family": "Giorda", "given": "Ezio", "initials": "E", "orcid": "0000-0002-5875-832X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6005bedf7cd44c678a5e50a999ba06dd.json"}}, {"family": "Scarsella", "given": "Marco", "initials": "M", "orcid": "0000-0002-3386-9664", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c8fe29ee7e764f6bb29092e11f52c6f9.json"}}, {"family": "Barbiera", "given": "Alessandra", "initials": "A", "orcid": "0000-0002-2051-2359", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c18e2aab6af747439958edfa9be888a7.json"}}, {"family": "Cadeddu", "given": "Giulia", "initials": "G", "orcid": "0000-0003-1841-8395", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6c209292faee4904bda06ce017551fd8.json"}}, {"family": "Colasanti", "given": "Marco", "initials": "M", "orcid": "0000-0002-5752-4943", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/479c78cbd64a455a9b7f5cbedd475fa0.json"}}, {"family": "Persichini", "given": "Tiziana", "initials": "T", "orcid": "0000-0001-8291-6706", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5d80e8c50c4f45b8b13eda46cbbc3067.json"}}, {"family": "Maeda", "given": "Kenji", "initials": "K", "orcid": "0000-0002-9080-5691", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9dc9c0792c6c44e29090a2683a73f884.json"}}, {"family": "Maya-Mendoza", "given": "Apolinar", "initials": "A", "orcid": "0000-0001-7452-9896", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8120d9952114478b9909d9906e0dd543.json"}}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/288939950c0c4c6393d35c84e5128b5f.json"}}, {"family": "Di Malta", "given": "Chiara", "initials": "C", "orcid": "0000-0001-6524-4354", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bef2e1eff2cf49f6ba6da220d8e76d2c.json"}}, {"family": "Locatelli", "given": "Franco", "initials": "F", "orcid": "0000-0002-7976-3654", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2687cc638c754f099e9a76deec1d8911.json"}}, {"family": "Zanivan", "given": "Sara", "initials": "S"}, {"family": "Ismail", "given": "Shehab", "initials": "S", "orcid": "0000-0002-4150-1077", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1587edc23d6043eb8c3be75259ef47e2.json"}}, {"family": "Ziviani", "given": "Elena", "initials": "E"}, {"family": "Cecconi", "given": "Francesco", "initials": "F", "orcid": "0000-0002-5614-4359", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1736eeb3ba3d4b0f80058b507487c5e1.json"}}], "type": "journal article", "published": "2025-10-03", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "11", "issue": "40", "pages": "eadw7376", "issn-l": "2375-2548"}, "abstract": "Mitochondrial homeostasis relies on a tight balance between mitochondrial biogenesis and degradation. Although mitophagy is one of the main pathways involved in the clearance of damaged or old mitochondria, its coordination with mitochondrial biogenesis is poorly characterized. Here, by unbiased approaches including last-generation liquid chromatography coupled to mass spectrometry and transcriptomics, we identify the protein phosphatase PP2A-B55\u03b1/PPP2R2A as a Parkin-dependent regulator of mitochondrial number. Upon mitochondrial damage, PP2A-B55\u03b1 determines the amplitude of mitophagy induction and execution by regulating both early and late mitophagy events. A few minutes after the insult, ULK1 is released from the inhibitory regulation of PP2A-B55\u03b1, whereas 2 to 4 hours later, PP2A-B55\u03b1 promotes the nuclear translocation of TFEB, the master regulator of autophagy and lysosome genes, to support mitophagy execution. Moreover, PP2A-B55\u03b1 controls a transcriptional program of mitochondrial biogenesis by stabilizing the Parkin substrate and PGC-1\u03b1 inhibitor PARIS. PP2A-B55\u03b1 targeting rescues neurodegenerative phenotypes in a fly model of Parkinson's disease, thus suggesting potential therapeutic application.", "doi": "10.1126/sciadv.adw7376", "pmid": "41042873", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12494018"}], "notes": [], "created": "2026-08-20T11:59:09.713Z", "modified": "2026-08-20T11:59:10.839Z"}, {"entity": "publication", "iuid": "6703dfab66c94278856a80aba8102dc7", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/6703dfab66c94278856a80aba8102dc7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/6703dfab66c94278856a80aba8102dc7"}}, "title": "NAD+ regulates nucleotide metabolism and genomic DNA replication.", "authors": [{"family": "Munk", "given": "Sebastian Howen Nesgaard", "initials": "SHN", "orcid": "0000-0002-4601-4833", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3c30767aaac5401696179217992498a0.json"}}, {"family": "Merchut-Maya", "given": "Joanna Maria", "initials": "JM"}, {"family": "Adelantado Rubio", "given": "Alba", "initials": "A"}, {"family": "Hall", "given": "Arnaldur", "initials": "A"}, {"family": "Pappas", "given": "George", "initials": "G"}, {"family": "Milletti", "given": "Giacomo", "initials": "G", "orcid": "0000-0003-2391-342X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/57f829170c13433d95819874b6fa3952.json"}}, {"family": "Lee", "given": "MyungHee", "initials": "M"}, {"family": "Johnsen", "given": "Lea Gi\u00f8rtz", "initials": "LG", "orcid": "0000-0002-0744-0899", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ddbbcb25f0b54c0288252fc69b1d53d9.json"}}, {"family": "Guldberg", "given": "Per", "initials": "P"}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/288939950c0c4c6393d35c84e5128b5f.json"}}, {"family": "Maya-Mendoza", "given": "Apolinar", "initials": "A", "orcid": "0000-0001-7452-9896", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8120d9952114478b9909d9906e0dd543.json"}}], "type": "journal article", "published": "2023-12-00", "journal": {"title": "Nat. Cell Biol.", "issn": "1476-4679", "volume": "25", "issue": "12", "pages": "1774-1786", "issn-l": "1465-7392"}, "abstract": "The intricate orchestration of enzymatic activities involving nicotinamide adenine dinucleotide (NAD+) is essential for maintaining metabolic homeostasis and preserving genomic integrity. As a co-enzyme, NAD+ plays a key role in regulating metabolic pathways, such as glycolysis and Kreb's cycle. ADP-ribosyltransferases (PARPs) and sirtuins rely on NAD+ to mediate post-translational modifications of target proteins. The activation of PARP1 in response to DNA breaks leads to rapid depletion of cellular NAD+ compromising cell viability. Therefore, the levels of NAD+ must be tightly regulated. Here we show that exogenous NAD+, but not its precursors, has a direct effect on mitochondrial activity. Short-term incubation with NAD+ boosts Kreb's cycle and the electron transport chain and enhances pyrimidine biosynthesis. Extended incubation with NAD+ results in depletion of pyrimidines, accumulation of purines, activation of the replication stress response and cell cycle arrest. Moreover, a combination of NAD+ and 5-fluorouridine selectively kills cancer cells that rely on de novo pyrimidine synthesis. We propose an integrated model of how NAD+ regulates nucleotide metabolism, with relevance to healthspan, ageing and cancer therapy.", "doi": "10.1038/s41556-023-01280-z", "pmid": "37957325", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10709141"}, {"db": "pii", "key": "10.1038/s41556-023-01280-z"}], "notes": [], "created": "2026-08-20T08:55:00.963Z", "modified": "2026-08-20T08:55:01.154Z"}, {"entity": "publication", "iuid": "b7277dd6ce53475d840bb9e1376bb4fd", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b7277dd6ce53475d840bb9e1376bb4fd.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b7277dd6ce53475d840bb9e1376bb4fd"}}, "title": "AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity.", "authors": [{"family": "Maiani", "given": "Emiliano", "initials": "E", "orcid": "0000-0003-1432-5394", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/28a7ce582c73429f8723c52f53c39136.json"}}, {"family": "Milletti", "given": "Giacomo", "initials": "G", "orcid": "0000-0003-2391-342X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/57f829170c13433d95819874b6fa3952.json"}}, {"family": "Nazio", "given": "Francesca", "initials": "F"}, {"family": "Holdgaard", "given": "S\u00f8s Gr\u00f8nb\u00e6k", "initials": "SG"}, {"family": "Bartkova", "given": "Jirina", "initials": "J"}, {"family": "Rizza", "given": "Salvatore", "initials": "S", "orcid": "0000-0001-7335-4684", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a6105a9f41af4c54bdf0b74c11a5701f.json"}}, {"family": "Cianfanelli", "given": "Valentina", "initials": "V", "orcid": "0000-0002-3857-9463", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ecd317d35f4142febdd006e4c19ecd3b.json"}}, {"family": "Lorente", "given": "Mar", "initials": "M"}, {"family": "Simoneschi", "given": "Daniele", "initials": "D", "orcid": "0000-0003-0448-4295", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9ef930f13dc34b09893d417f99a1822c.json"}}, {"family": "Di Marco", "given": "Miriam", "initials": "M"}, {"family": "D'Acunzo", "given": "Pasquale", "initials": "P", "orcid": "0000-0001-7237-0076", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ae134a21c0f44416a8f7825d3985d465.json"}}, {"family": "Di Leo", "given": "Luca", "initials": "L", "orcid": "0000-0002-2419-2196", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b38f503dd3d34de885137408e2b10daf.json"}}, {"family": "Rasmussen", "given": "Rikke", "initials": "R"}, {"family": "Montagna", "given": "Costanza", "initials": "C"}, {"family": "Raciti", "given": "Marilena", "initials": "M"}, {"family": "De Stefanis", "given": "Cristiano", "initials": "C"}, {"family": "Gabicagogeascoa", "given": "Estibaliz", "initials": "E"}, {"family": "Rona", "given": "Gergely", "initials": "G"}, {"family": "Salvador", "given": "N\u00e9lida", "initials": "N"}, {"family": "Pupo", "given": "Emanuela", "initials": "E"}, {"family": "Merchut-Maya", "given": "Joanna Maria", "initials": "JM"}, {"family": "Daniel", "given": "Colin J", "initials": "CJ"}, {"family": "Carinci", "given": "Marianna", "initials": "M"}, {"family": "Cesarini", "given": "Valeriana", "initials": "V"}, {"family": "O'sullivan", "given": "Alfie", "initials": "A"}, {"family": "Jeong", "given": "Yeon-Tae", "initials": "YT"}, {"family": "Bordi", "given": "Matteo", "initials": "M", "orcid": "0000-0001-8207-8546", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9c34176b2b1141f6a41d23f49de8e4ec.json"}}, {"family": "Russo", "given": "Francesco", "initials": "F"}, {"family": "Campello", "given": "Silvia", "initials": "S", "orcid": "0000-0003-0536-2484", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2efe505b1c654d21a2e1bc7747b8d739.json"}}, {"family": "Gallo", "given": "Angela", "initials": "A"}, {"family": "Filomeni", "given": "Giuseppe", "initials": "G", "orcid": "0000-0002-2719-1412", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5d3fdc6c498f4104a43fa2d2198ef484.json"}}, {"family": "Lanzetti", "given": "Letizia", "initials": "L", "orcid": "0000-0001-7541-5524", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b2da7f657203439d8bc75b048c181dd2.json"}}, {"family": "Sears", "given": "Rosalie C", "initials": "RC", "orcid": "0000-0003-1558-2413", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6cc5e16675434a58b04b0db6ad618167.json"}}, {"family": "Hamerlik", "given": "Petra", "initials": "P"}, {"family": "Bartolazzi", "given": "Armando", "initials": "A", "orcid": "0000-0001-7820-5127", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2d5a218ebfcd45b4aae83562b6801f33.json"}}, {"family": "Hynds", "given": "Robert E", "initials": "RE", "orcid": "0000-0002-2170-8791", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d363c63598224cb0bd24dffc46d0d3eb.json"}}, {"family": "Pearce", "given": "David R", "initials": "DR", "orcid": "0000-0001-8443-2924", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6e102ef6912747fba625f94fb0d8b774.json"}}, {"family": "Swanton", "given": "Charles", "initials": "C", "orcid": "0000-0002-4299-3018", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e624db9004da4812a607b34b20cea0e7.json"}}, {"family": "Pagano", "given": "Michele", "initials": "M"}, {"family": "Velasco", "given": "Guillermo", "initials": "G", "orcid": "0000-0002-1994-2386", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1bc733f7578d48739bceff94fbc156cb.json"}}, {"family": "Papaleo", "given": "Elena", "initials": "E"}, {"family": "De Zio", "given": "Daniela", "initials": "D", "orcid": "0000-0002-9454-402X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9493b5e7aab54818b2142490af5ea7b9.json"}}, {"family": "Maya-Mendoza", "given": "Apolinar", "initials": "A", "orcid": "0000-0001-7452-9896", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8120d9952114478b9909d9906e0dd543.json"}}, {"family": "Locatelli", "given": "Franco", "initials": "F"}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/288939950c0c4c6393d35c84e5128b5f.json"}}, {"family": "Cecconi", "given": "Francesco", "initials": "F", "orcid": "0000-0002-5614-4359", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1736eeb3ba3d4b0f80058b507487c5e1.json"}}], "type": "journal article", "published": "2021-04-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "592", "issue": "7856", "pages": "799-803", "issn-l": "0028-0836"}, "abstract": "Mammalian development, adult tissue homeostasis and the avoidance of severe diseases including cancer require a properly orchestrated cell cycle, as well as error-free genome maintenance. The key cell-fate decision to replicate the genome is controlled by two major signalling pathways that act in parallel-the MYC pathway and the cyclin D-cyclin-dependent kinase (CDK)-retinoblastoma protein (RB) pathway1,2. Both MYC and the cyclin D-CDK-RB axis are commonly deregulated in cancer, and this is associated with increased genomic instability. The autophagic tumour-suppressor protein AMBRA1 has been linked to the control of cell proliferation, but the underlying molecular mechanisms remain poorly understood. Here we show that AMBRA1 is an upstream master regulator of the transition from G1 to S phase and thereby prevents replication stress. Using a combination of cell and molecular approaches and in vivo models, we reveal that AMBRA1 regulates the abundance of D-type cyclins by mediating their degradation. Furthermore, by controlling the transition from G1 to S phase, AMBRA1 helps to maintain genomic integrity during DNA replication, which counteracts developmental abnormalities and tumour growth. Finally, we identify the CHK1 kinase as a potential therapeutic target in AMBRA1-deficient tumours. These results advance our understanding of the control of replication-phase entry and genomic integrity, and identify the AMBRA1-cyclin D pathway as a crucial cell-cycle-regulatory mechanism that is deeply interconnected with genomic stability in embryonic development and tumorigenesis.", "doi": "10.1038/s41586-021-03422-5", "pmid": "33854232", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1776644"}, {"db": "pmc", "key": "PMC8864551"}, {"db": "pii", "key": "10.1038/s41586-021-03422-5"}], "notes": [], "created": "2026-08-20T08:56:26.998Z", "modified": "2026-08-20T08:57:56.476Z"}]}