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Oxidative stress modulates rearrangement of endoplasmic reticulum-mitochondria contacts and calcium dysregulation in a Friedreich's ataxia model
- Source :
- Redox Biology, Vol 37, Iss, Pp 101762-(2020), Redox Biology
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
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.<br />Graphical abstract Image 1
- Subjects :
- 0301 basic medicine
Ataxia
Clinical Biochemistry
Lipid peroxidation
chemistry.chemical_element
Mitochondrion
Calcium
Endoplasmic Reticulum
Biochemistry
03 medical and health sciences
0302 clinical medicine
MAMs
medicine
Animals
Vitamin E
Mitochondrial calcium uptake
lcsh:QH301-705.5
Calcium signaling
lcsh:R5-920
biology
Frataxin
Endoplasmic reticulum
Organic Chemistry
N-acetylcysteine
Mitochondria
Cell biology
Oxidative Stress
Drosophila melanogaster
030104 developmental biology
chemistry
lcsh:Biology (General)
Friedreich Ataxia
biology.protein
medicine.symptom
Cellular model
lcsh:Medicine (General)
030217 neurology & neurosurgery
Research Paper
Subjects
Details
- Language :
- English
- ISSN :
- 22132317
- Volume :
- 37
- Database :
- OpenAIRE
- Journal :
- Redox Biology
- Accession number :
- edsair.doi.dedup.....5d233a8b802b13d019f1d83087e9b7da