6533b823fe1ef96bd127ed78

RESEARCH PRODUCT

Disarrangement of Endoplasmic reticulum-mitochondria communication impairs Ca2+ homeostasis in FRDA

Stephan SchneuwlyPilar Gonzalez-caboJuan A. NavarroTamara Lapeña-luzónLaura R. RodríguezPablo Calap-quintanaFederico V. Pallardó

subject

0303 health sciencesbiologyEndoplasmic reticulumLipid metabolismMitochondrionbiology.organism_classification3. Good healthCell biology03 medical and health sciences0302 clinical medicineFrataxinbiology.proteinMitochondrial calcium uptakeCellular modelDrosophila melanogaster030217 neurology & neurosurgery030304 developmental biologyCalcium signaling

description

AbstractFriedreich ataxia (FRDA) is a neurodegenerative disorder characterized by neuromuscular and neurological manifestations. It is caused by mutations in gene FXN, 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, an analysis of calcium management and of 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.

yearjournalcountryeditionlanguage
2020-03-29
https://doi.org/10.1101/2020.03.27.011528