Artículo
CFTR chloride channel activity modulates the mitochondrial morphology in cultured epithelial cells
García, Rocío; Falduti, Camila; Clauzure, Mariangeles
; Jara, Ana Raquel; Massip Copiz, María Macarena
; Aguilar, María de los Ángeles; Santa Coloma, Tomás Antonio
; Valdivieso, Ángel Gabriel
Fecha de publicación:
06/2021
Editorial:
Pergamon-Elsevier Science Ltd
Revista:
International Journal of Biochemistry and Cellular Biology
ISSN:
1357-2725
e-ISSN:
1878-5875
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The impairment of the CFTR channel activity, a cAMP-activated chloride (Cl−) channel responsible for cystic fibrosis (CF), has been associated with a variety of mitochondrial alterations such as modified gene expression, impairment in oxidative phosphorylation, increased reactive oxygen species (ROS), and a disbalance in calcium homeostasis. The mechanisms by which these processes occur in CF are not fully understood. Previously, we demonstrated a reduced MTND4 expression and a failure in the mitochondrial complex I (mCx-I) activity in CF cells. Here we hypothesized that the activity of CFTR might modulate the mitochondrial fission/fusion balance, explaining the decreased mCx-I. The mitochondrial morphology and the levels of mitochondrial dynamic proteins MFN1 and DRP1 were analysed in IB3−1 CF cells, and S9 (IB3−1 expressing wt-CFTR), and C38 (IB3−1 expressing a truncated functional CFTR) cells. The mitochondrial morphology of IB3−1 cells compared to S9 and C38 cells showed that the impaired CFTR activity induced a fragmented mitochondrial network with increased rounded mitochondria and shorter branches. Similar results were obtained by using the CFTR pharmacological inhibitors CFTR(inh)-172 and GlyH101 on C38 cells. These morphological changes were accompanied by modifications in the levels of the mitochondrial dynamic proteins MFN1, DRP1, and p(616)-DRP1. IB3−1 CF cells treated with Mdivi-1, an inhibitor of mitochondrial fission, restored the mCx-I activity to values similar to those seen in S9 and C38 cells. These results suggest that the mitochondrial fission/fusion balance is regulated by the CFTR activity and might be a potential target to treat the impaired mCx-I activity in CF.
Palabras clave:
CFTR
,
CYSTIC FIBROSIS
,
DRP1
,
MDIVI-1
,
MFN1
,
MITOCHONDRIAL DYNAMICS
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(BIOMED)
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Articulos(CCT - PATAGONIA CONFLUENCIA)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - PATAGONIA CONFLUENCIA
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - PATAGONIA CONFLUENCIA
Citación
García, Rocío; Falduti, Camila; Clauzure, Mariangeles; Jara, Ana Raquel; Massip Copiz, María Macarena; et al.; CFTR chloride channel activity modulates the mitochondrial morphology in cultured epithelial cells; Pergamon-Elsevier Science Ltd; International Journal of Biochemistry and Cellular Biology; 135; 6-2021; 1-10
Compartir
Altmétricas