Publications

Authors:

Magrinelli, Francesca; Tesson, Christelle; Angelova, Plamena R; Rodriguez, Jose A; Scardamaglia, Annarita; O'Callaghan, Benjamin; Lowe, Simon A; Salazar-Villacorta, Ainara; Chung, Brian Hon-Yin; Jaconelli, Matthew; Vona, Barbara; Esteras, Noemi; Mammana, Angela; Shimazu, Junko; Kwong, Anna Ka-Yee; Courtin, Thomas; Alavi, Shahryar; Maroofian, Reza; Nirujogi, Raja; Severino, Mariasavina; Monfrini, Edoardo; Rocca, Clarissa; Lewis, Patrick A; Efthymiou, Stephanie; Buchert, Rebecca; Sofan, Linda; Lis, Pawel; Pinon, Chloé; Breedveld, Guido J; Chui, Martin Man-Chun; Murphy, David; Pitz, Vanessa; Makarious, Mary B; Baiardi, Simone; Volin, Marina; Cassar, Marlene; Hassan, Bassem A; Iftikhar, Sana; Bauer, Peter; Tinazzi, Michele; Svetel, Marina; Samanci, Bedia; Hanağası, Haşmet A; Bilgiç, Basar; Cavallieri, Francesco; Santangelo, Mario; Obeso, José A; Kurtis, Monica M; Cogan, Guillaume; Kiziltan, Güneş; Gül-Demirkale, Tuğçe; Tireli, Hülya; Yüksel, Gülbün A; Yalçın-Cakmakli, Gül; Elibol, Bülent; Barišić, Nina; Ng, Earny Wei-Sen; Fan, Sze-Shing; Hershkovitz, Tova; Weiss, Karin; Alvi, Javeria Raza; Sultan, Tipu; Alkhawaja, Issam Azmi; Froukh, Tawfiq; Alrukban, Hadeel Abdollah E; Anjum, Muhammad Nadeem; Saeed, Anjum; Cheema, Huma Arshad; Fauth, Christine; Schatz, Ulrich A; Zöggeler, Thomas; Zech, Michael; Stals, Karen; Varghese, Vinod; Gandhi, Sonia; Blauwendraat, Cornelis; Hardy, John A; Di Fonzo, Alessio; Bonifati, Vincenzo; Haack, Tobias B; Bertoli-Avella, Aida M; Lesage, Suzanne; Başak, Ayşe Nazlı; Steinfeld, Robert; Parchi, Piero; Jepson, James E C; Alessi, Dario R; Brice, Alexis; Steller, Hermann; Abramov, Andrey Y; Bhatia, Kailash P; Houlden, Henry

Title:

Variants in the proteasome regulator PSMF1 cause a phenotypic spectrum from parkinsonism to perinatal lethality

Year:

2026

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

Elettronico

Referee:

Sì

Name of journal:

NATURE COMMUNICATIONS

ISSN of journal:

2041-1723

N° Volume:

First published online: 15 April 2026

Page numbers:

1-55

Keyword:

mitochondria; mutation; neurodevelopmental disorders; Parkinson's disease; proteasome

Short description of contents:

Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson's disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here we identify PSMF1 as a gene implicated in parkinsonism and childhood neurodegeneration. We find that biallelic PSMF1 missense and loss-of-function variants co-segregate with phenotypes from early-onset PD to perinatal lethality with neurological manifestations across 18 pedigrees with 25 affected subjects, showing clear genotype-phenotype correlation. PSMF1 encodes the proteasome regulator PSMF1/hPI31, a highly conserved, ubiquitously expressed partner of the 20S proteasome and neurodegeneration-associated F-box-O 7 and valosin-containing proteins. We demonstrate that PSMF1 variants may affect proteasomal abundance and assembly, and are associated with alterations of mitochondrial membrane potential, respiration, dynamics and mitophagy in patient-derived fibroblasts. Furthermore, Drosophila and mouse models of PI31 loss of function exhibit age-dependent motor impairment, as well as brain-wide mitochondrial membrane depolarization and dopaminergic neurodegeneration in aged flies, and diffuse gliosis in mice. Collectively, our findings unequivocally link defective PSMF1/hPI31 to early-onset parkinsonism and neurodegeneration, and suggest proteasomal and mitochondrial dysfunction as pathogenic contributors.

Web page:

https://doi.org/10.1038/s41467-026-71351-w

Product ID:

150868

Handle IRIS:

11562/1189850

Last Modified:

April 23, 2026

Bibliographic citation:

Magrinelli, Francesca; Tesson, Christelle; Angelova, Plamena R; Rodriguez, Jose A; Scardamaglia, Annarita; O'Callaghan, Benjamin; Lowe, Simon A; Salazar-Villacorta, Ainara; Chung, Brian Hon-Yin; Jaconelli, Matthew; Vona, Barbara; Esteras, Noemi; Mammana, Angela; Shimazu, Junko; Kwong, Anna Ka-Yee; Courtin, Thomas; Alavi, Shahryar; Maroofian, Reza; Nirujogi, Raja; Severino, Mariasavina; Monfrini, Edoardo; Rocca, Clarissa; Lewis, Patrick A; Efthymiou, Stephanie; Buchert, Rebecca; Sofan, Linda; Lis, Pawel; Pinon, Chloé; Breedveld, Guido J; Chui, Martin Man-Chun; Murphy, David; Pitz, Vanessa; Makarious, Mary B; Baiardi, Simone; Volin, Marina; Cassar, Marlene; Hassan, Bassem A; Iftikhar, Sana; Bauer, Peter; Tinazzi, Michele; Svetel, Marina; Samanci, Bedia; Hanağası, Haşmet A; Bilgiç, Basar; Cavallieri, Francesco; Santangelo, Mario; Obeso, José A; Kurtis, Monica M; Cogan, Guillaume; Kiziltan, Güneş; Gül-Demirkale, Tuğçe; Tireli, Hülya; Yüksel, Gülbün A; Yalçın-Cakmakli, Gül; Elibol, Bülent; Barišić, Nina; Ng, Earny Wei-Sen; Fan, Sze-Shing; Hershkovitz, Tova; Weiss, Karin; Alvi, Javeria Raza; Sultan, Tipu; Alkhawaja, Issam Azmi; Froukh, Tawfiq; Alrukban, Hadeel Abdollah E; Anjum, Muhammad Nadeem; Saeed, Anjum; Cheema, Huma Arshad; Fauth, Christine; Schatz, Ulrich A; Zöggeler, Thomas; Zech, Michael; Stals, Karen; Varghese, Vinod; Gandhi, Sonia; Blauwendraat, Cornelis; Hardy, John A; Di Fonzo, Alessio; Bonifati, Vincenzo; Haack, Tobias B; Bertoli-Avella, Aida M; Lesage, Suzanne; Başak, Ayşe Nazlı; Steinfeld, Robert; Parchi, Piero; Jepson, James E C; Alessi, Dario R; Brice, Alexis; Steller, Hermann; Abramov, Andrey Y; Bhatia, Kailash P; Houlden, Henry, Variants in the proteasome regulator PSMF1 cause a phenotypic spectrum from parkinsonism to perinatal lethality «NATURE COMMUNICATIONS» , vol. First published online: 15 April 2026 , 2026 , pp. 1-55

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo