Portal de investigación
Oxidative stress modulates rearrangement of endoplasmic reticulum-mitochondria contacts and calcium dysregulation in a Friedreich's ataxia model.
Fecha de publicación:
Fecha Ahead of Print:
Autores de INCLIVA
Participantes ajenos a INCLIVA
- Schneuwly, Stephan
Grupos y Plataformas de I+D+i
Abstract
Friedreich ataxia (FRDA) is a neurodegenerative disorder characterized by neuromuscular and neurological manifestations. It is caused by mutations in the FXN gene, which results in loss of the mitochondrial protein frataxin. Endoplasmic Reticulum-mitochondria associated membranes (MAMs) are inter-organelle structures involved in the regulation of essential cellular processes, including lipid metabolism and calcium signaling. In the present study, we have analyzed in both, unicellular and multicellular models of FRDA, calcium management and integrity of MAMs. We observed that function of MAMs is compromised in our cellular model of FRDA, which was improved upon treatment with antioxidants. In agreement, promoting mitochondrial calcium uptake was sufficient to restore several defects caused by frataxin deficiency in Drosophila Melanogaster. Remarkably, our findings describe for the first time frataxin as a member of the protein network of MAMs, where interacts with two of the main proteins implicated in endoplasmic reticulum-mitochondria communication. These results suggest a new role of frataxin, indicate that FRDA goes beyond mitochondrial defects and highlight MAMs as novel therapeutic candidates to improve patient's conditions.
© 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Datos de la publicación
- ISSN/ISSNe:
- 2213-2317, 2213-2317
- Tipo:
- Article
- Páginas:
- 101762-101762
- PubMed:
- 33128998
Redox Biology ELSEVIER SCIENCE BV
Citas Recibidas en Web of Science: 36
Documentos
Filiaciones
Keywords
- MAMs; Frataxin; Calcium; Lipid peroxidation; Vitamin E; N-acetylcysteine
Financiación
Proyectos y Estudios Clínicos
CDEI-04/20-C GENT JUAN ANTONIO NAVARRO (2019/199) CONTRATO
Investigador Principal: JUAN ANTONIO NAVARRO LANGA
2019/199C . CONSELLERIA DE SANIDAD . 2020
Cita
Rodriguez LR,Calap P,Lapena T,Pallardo FV,Schneuwly S,Navarro JA,Gonzalez P. Oxidative stress modulates rearrangement of endoplasmic reticulum-mitochondria contacts and calcium dysregulation in a Friedreich's ataxia model. Redox Biol. 2020. 37. p. 101762-101762. IF:11,799. (1).
Oxidative stress modulates rearrangement of endoplasmic reticulum-mitochondria contacts and calcium dysregulation in a Friedreich's ataxia model. Rodriguez LR, Calap P, Lapena T, Pallardo FV, Schneuwly S, Navarro JA, Gonzalez P. Redox Biology. 2020 octubre 16. 37101762-101762. DOI:10.1016/j.redox.2020.101762. PMID:33128998.
