ETNK1 mutations induce a mutator phenotype that can be reverted with phosphoethanolamine

Diletta Fontana, Mario Mauri, Rossella Renso, Mattia Docci, Ilaria Crespiatico, Lisa M. Røst, Mi Jang, Antonio Niro, Deborah D’Aliberti, Luca Massimino, Mayla Bertagna, Giovanni Zambrotta, Mario Bossi, Stefania Citterio, Barbara Crescenzi, Francesca Fanelli, Valeria Cassina, Roberta Corti, Domenico Salerno, Luca Nardo, Clizia Chinello, Francesco Mantegazza, Cristina Mecucci, Fulvio Magni, Guido Cavaletti, Per Bruheim, Delphine Rea, Steen Larsen, Carlo Gambacorti-Passerini and Rocco Piazza ()
Additional contact information
Diletta Fontana: University of Milano - Bicocca
Mario Mauri: University of Milano - Bicocca
Rossella Renso: University of Milano - Bicocca
Mattia Docci: University of Milano - Bicocca
Ilaria Crespiatico: University of Milano - Bicocca
Lisa M. Røst: Norwegian University of Science and Technology
Mi Jang: Norwegian University of Science and Technology
Antonio Niro: University of Milano - Bicocca
Deborah D’Aliberti: University of Milano - Bicocca
Luca Massimino: University of Milano - Bicocca
Mayla Bertagna: University of Milano - Bicocca
Giovanni Zambrotta: University of Milano - Bicocca
Mario Bossi: University of Milano - Bicocca
Stefania Citterio: University of Milano - Bicocca
Barbara Crescenzi: University of Perugia
Francesca Fanelli: University of Modena and Reggio Emilia
Valeria Cassina: University of Milano - Bicocca
Roberta Corti: University of Milano - Bicocca
Domenico Salerno: University of Milano - Bicocca
Luca Nardo: University of Milano - Bicocca
Clizia Chinello: University of Milano - Bicocca
Francesco Mantegazza: University of Milano - Bicocca
Cristina Mecucci: University of Perugia
Fulvio Magni: University of Milano - Bicocca
Guido Cavaletti: University of Milano - Bicocca
Per Bruheim: Norwegian University of Science and Technology
Delphine Rea: Hôpital Saint-Louis
Steen Larsen: University of Copenhagen
Carlo Gambacorti-Passerini: University of Milano - Bicocca
Rocco Piazza: University of Milano - Bicocca

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract Recurrent somatic mutations in ETNK1 (Ethanolamine-Kinase-1) were identified in several myeloid malignancies and are responsible for a reduced enzymatic activity. Here, we demonstrate in primary leukemic cells and in cell lines that mutated ETNK1 causes a significant increase in mitochondrial activity, ROS production, and Histone H2AX phosphorylation, ultimately driving the increased accumulation of new mutations. We also show that phosphoethanolamine, the metabolic product of ETNK1, negatively controls mitochondrial activity through a direct competition with succinate at mitochondrial complex II. Hence, reduced intracellular phosphoethanolamine causes mitochondria hyperactivation, ROS production, and DNA damage. Treatment with phosphoethanolamine is able to counteract complex II hyperactivation and to restore a normal phenotype.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-19721-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19721-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-19721-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().