CFTR chloride channel activity modulates the mitochondrial morphology in cultured epithelial cells
Abstract: 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...
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| Formato: | Artículo |
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Elsevier
2022
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| Acceso en línea: | https://repositorio.uca.edu.ar/handle/123456789/14597 |
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I33-R139-123456789-145972023-11-23T17:15:57Z CFTR chloride channel activity modulates the mitochondrial morphology in cultured epithelial cells García Solcá, Rocío Falduti, Camila Clauzure, Mariángeles Jara, Raquel Massip Copiz, María M. Aguilar, María de los Angeles Santa Coloma, Tomás Antonio Valdivieso, Ángel Gabriel FIBROSIS QUISTICA DINAMICA MITOCONDRIAL REGULADOR DE CONDUCTANCIA DE TRANSMEMBRANA DE FIBROSIS QUISTICA CELULAS EPITELIALES DRP1 MFN1 Mdivi-1 Abstract: 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. 2022-08-02T15:07:28Z 2022-08-02T15:07:28Z 2021 Artículo García Solcá, R. et al. CFTR chloride channel activity modulates the mitochondrial morphology in cultured epithelial cells [en línea]. International Journal of Biochemistry and Cell Biology. 2021, 135, 105976. doi: 10.1016/j.biocel.2021.105976. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/14597 1357-2725 https://repositorio.uca.edu.ar/handle/123456789/14597 10.1016/j.biocel.2021.105976 33845203 eng Acceso restringido http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Elsevier International Journal of Biochemistry and Cell Biology , Vol. 135, 105976, 2021 |
| institution |
Universidad Católica Argentina |
| institution_str |
I-33 |
| repository_str |
R-139 |
| collection |
Repositorio Institucional de la Universidad Católica Argentina (UCA) |
| language |
Inglés |
| topic |
FIBROSIS QUISTICA DINAMICA MITOCONDRIAL REGULADOR DE CONDUCTANCIA DE TRANSMEMBRANA DE FIBROSIS QUISTICA CELULAS EPITELIALES DRP1 MFN1 Mdivi-1 |
| spellingShingle |
FIBROSIS QUISTICA DINAMICA MITOCONDRIAL REGULADOR DE CONDUCTANCIA DE TRANSMEMBRANA DE FIBROSIS QUISTICA CELULAS EPITELIALES DRP1 MFN1 Mdivi-1 García Solcá, Rocío Falduti, Camila Clauzure, Mariángeles Jara, Raquel Massip Copiz, María M. Aguilar, María de los Angeles Santa Coloma, Tomás Antonio Valdivieso, Ángel Gabriel CFTR chloride channel activity modulates the mitochondrial morphology in cultured epithelial cells |
| topic_facet |
FIBROSIS QUISTICA DINAMICA MITOCONDRIAL REGULADOR DE CONDUCTANCIA DE TRANSMEMBRANA DE FIBROSIS QUISTICA CELULAS EPITELIALES DRP1 MFN1 Mdivi-1 |
| description |
Abstract: 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. |
| format |
Artículo |
| author |
García Solcá, Rocío Falduti, Camila Clauzure, Mariángeles Jara, Raquel Massip Copiz, María M. Aguilar, María de los Angeles Santa Coloma, Tomás Antonio Valdivieso, Ángel Gabriel |
| author_facet |
García Solcá, Rocío Falduti, Camila Clauzure, Mariángeles Jara, Raquel Massip Copiz, María M. Aguilar, María de los Angeles Santa Coloma, Tomás Antonio Valdivieso, Ángel Gabriel |
| author_sort |
García Solcá, Rocío |
| title |
CFTR chloride channel activity modulates the mitochondrial morphology in cultured epithelial cells |
| title_short |
CFTR chloride channel activity modulates the mitochondrial morphology in cultured epithelial cells |
| title_full |
CFTR chloride channel activity modulates the mitochondrial morphology in cultured epithelial cells |
| title_fullStr |
CFTR chloride channel activity modulates the mitochondrial morphology in cultured epithelial cells |
| title_full_unstemmed |
CFTR chloride channel activity modulates the mitochondrial morphology in cultured epithelial cells |
| title_sort |
cftr chloride channel activity modulates the mitochondrial morphology in cultured epithelial cells |
| publisher |
Elsevier |
| publishDate |
2022 |
| url |
https://repositorio.uca.edu.ar/handle/123456789/14597 |
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