Artículo
Endogenous formaldehyde scavenges cellular glutathione resulting in redox disruption and cytotoxicity
Umansky, Carla
; Morellato, Agustín Ezequiel
; Rieckher, Matthias; Scheidegger, Marco Adrian
; Martinefski, Manuela Romina
; Fernandez, Gabriela A.; Pak, Oleg; Kolesnikova, Ksenia; Reingruber, Hernán
; Bollini, Mariela
; Crossan, Gerry P.; Sommer, Natascha; Monge, Maria Eugenia
; Schumacher, Björn; Pontel, Lucas Blas
Fecha de publicación:
02/2022
Editorial:
Springer
Revista:
Nature Communications
ISSN:
2041-1723
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Formaldehyde (FA) is a ubiquitous endogenous and environmental metabolite that is thought to exert cytotoxicity through DNA and DNA-protein crosslinking, likely contributing to the onset of the human DNA repair condition Fanconi Anaemia. Mutations in the genes coding for FA detoxifying enzymes underlie a human inherited bone marrow failure syndrome (IBMFS), even in the presence of functional DNA repair, raising the question of whether FA causes relevant cellular damage beyond genotoxicity. Here, we report that FA triggers cellular redox imbalance in human cells and in Caenorhabditis elegans. Mechanistically, FA reacts with the redox-active thiol group of glutathione (GSH), altering the GSH:GSSG ratio and causing oxidative stress. FA cytotoxicity is prevented by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR), which metabolizes FA-GSH products, lastly yielding reduced GSH. Furthermore, we show that GSH synthesis protects human cells from FA, indicating an active role of GSH in preventing FA toxicity. These findings might be relevant for patients carrying mutations in FA-detoxification systems and could suggest therapeutic benefits from thiol-rich antioxidants like N-acetyl-L-cysteine.
Palabras clave:
FORMALDEHYDE
,
ALCOHOL DEHYDROGENASE 5
,
GLUTATHIONE
,
FANCONI ANAEMIA
,
ROS
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Articulos(CIBION)
Articulos de CENTRO DE INVESTIGACIONES EN BIONANOCIENCIAS "ELIZABETH JARES ERIJMAN"
Articulos de CENTRO DE INVESTIGACIONES EN BIONANOCIENCIAS "ELIZABETH JARES ERIJMAN"
Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Umansky, Carla; Morellato, Agustín Ezequiel; Rieckher, Matthias; Scheidegger, Marco Adrian; Martinefski, Manuela Romina; et al.; Endogenous formaldehyde scavenges cellular glutathione resulting in redox disruption and cytotoxicity; Springer; Nature Communications; 13; 1; 2-2022; 1-15
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