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Article

DRP1 Inhibition Rescues Mitochondrial Integrity and Excessive Apoptosis in CS-A Disease Cell Models

1
Institute of Crystallography, Consiglio Nazionale delle Ricerche, 00015 Rome, Italy
2
Department of Environment and Health, Istituto Superiore di Sanità, 00161 Rome, Italy
3
Core Facilities, Istituto Superiore di Sanità, 00161 Rome, Italy
4
Research Coordination and Support Service, Istituto Superiore di Sanità, 00161 Rome, Italy
5
National Center for Research and Preclinical and Clinical Evaluation of Drugs, Istituto Superiore di Sanità, 00161 Rome, Italy
6
Department of Biology, Tor Vergata University, 00133 Rome, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: David M Wilson
Int. J. Mol. Sci. 2021, 22(13), 7123; https://doi.org/10.3390/ijms22137123
Received: 9 June 2021 / Revised: 25 June 2021 / Accepted: 28 June 2021 / Published: 1 July 2021
(This article belongs to the Special Issue Genome Stability and Neurological Disease)
Cockayne syndrome group A (CS-A) is a rare recessive progeroid disorder characterized by sun sensitivity and neurodevelopmental abnormalities. Cells derived from CS-A patients present as pathological hallmarks excessive oxidative stress, mitochondrial fragmentation and apoptosis associated with hyperactivation of the mitochondrial fission dynamin related protein 1 (DRP1). In this study, by using human cell models we further investigated the interplay between DRP1 and CSA and we determined whether pharmacological or genetic inhibition of DRP1 affects disease progression. Both reactive oxygen and nitrogen species are in excess in CS-A cells and when the mitochondrial translocation of DRP1 is inhibited a reduction of these species is observed together with a recovery of mitochondrial integrity and a significant decrease of apoptosis. This study indicates that the CSA-driven modulation of DRP1 pathway is key to control mitochondrial homeostasis and apoptosis and suggests DRP1 as a potential target in the treatment of CS patients. View Full-Text
Keywords: cockayne syndrome; mitochondrial dysfunction; apoptosis; MDIVI-1 cockayne syndrome; mitochondrial dysfunction; apoptosis; MDIVI-1
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MDPI and ACS Style

Pascucci, B.; Spadaro, F.; Pietraforte, D.; Nuccio, C.D.; Visentin, S.; Giglio, P.; Dogliotti, E.; D’Errico, M. DRP1 Inhibition Rescues Mitochondrial Integrity and Excessive Apoptosis in CS-A Disease Cell Models. Int. J. Mol. Sci. 2021, 22, 7123. https://doi.org/10.3390/ijms22137123

AMA Style

Pascucci B, Spadaro F, Pietraforte D, Nuccio CD, Visentin S, Giglio P, Dogliotti E, D’Errico M. DRP1 Inhibition Rescues Mitochondrial Integrity and Excessive Apoptosis in CS-A Disease Cell Models. International Journal of Molecular Sciences. 2021; 22(13):7123. https://doi.org/10.3390/ijms22137123

Chicago/Turabian Style

Pascucci, Barbara, Francesca Spadaro, Donatella Pietraforte, Chiara D. Nuccio, Sergio Visentin, Paola Giglio, Eugenia Dogliotti, and Mariarosaria D’Errico. 2021. "DRP1 Inhibition Rescues Mitochondrial Integrity and Excessive Apoptosis in CS-A Disease Cell Models" International Journal of Molecular Sciences 22, no. 13: 7123. https://doi.org/10.3390/ijms22137123

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