Rodriguez, Laura R. and Calap-Quintana, Pablo and Lapena-Luzon, Tamara and Pallardo, Federico and Schneuwly, Stephan and Navarro, Juan A. and Gonzalez-Cabo, Pilar (2020) Oxidative stress modulates rearrangement of endoplasmic reticulum-mitochondria contacts and calcium dysregulation in a Friedreich's ataxia model. REDOX BIOLOGY, 37: 101762. ISSN 2213-2317,
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ALTERED LIPID-METABOLISM; IRON-SULFUR CLUSTERS; MOLECULAR-MECHANISMS; MOUSE MODELS; FRATAXIN; HOMEOSTASIS; UNIPORTER; MEMBRANES; HEME; LOCALIZATION; MAMs; Frataxin; Calcium; Lipid peroxidation; Vitamin E; N-acetylcysteine |
| Subjects: | 500 Science > 570 Life sciences 500 Science > 590 Zoological sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Zoologie Biology, Preclinical Medicine > Institut für Zoologie > Entwicklungsbiologie (Prof. Dr. Stephan Schneuwly) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Mar 2021 08:18 |
| Last Modified: | 09 Mar 2021 08:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43615 |
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