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Angebault 2018 Sci Signal

From Bioblast
Publications in the MiPMap
Angebault C, Fauconnier J, Patergnani S, Rieusset J, Danese A, Affortit CA, Jagodzinska J, Mรฉgy C, Quiles M, Cazevieille C, Korchagina J, Bonnet-Wersinger D, Milea D, Hamel C, Pinton P, Thiry M, Lacampagne A, Delprat B, Delettre C (2018) ER-mitochondria cross-talk is regulated by the Ca2+ sensor NCS1 and is impaired in Wolfram syndrome. Sci Signal 11:eaaq1380.

ยป PMID: 30352948

Angebault C, Fauconnier J, Patergnani S, Rieusset J, Danese A, Affortit CA, Jagodzinska J, Megy C, Quiles M, Cazevieille C, Korchagina J, Bonnet-Wersinger D, Milea D, Hamel C, Pinton P, Thiry M, Lacampagne A, Delprat B, Delettre C (2018) Sci Signal

Abstract: Communication between the endoplasmic reticulum (ER) and mitochondria plays a pivotal role in Ca2+ signaling, energy metabolism, and cell survival. Dysfunction in this cross-talk leads to metabolic and neurodegenerative diseases. Wolfram syndrome is a fatal neurodegenerative disease caused by mutations in the ER-resident protein WFS1. Here, we showed that WFS1 formed a complex with neuronal calcium sensor 1 (NCS1) and inositol 1,4,5-trisphosphate receptor (IP3R) to promote Ca2+ transfer between the ER and mitochondria. In addition, we found that NCS1 abundance was reduced in WFS1-null patient fibroblasts, which showed reduced ER-mitochondria interactions and Ca2+ exchange. Moreover, in WFS1-deficient cells, NCS1 overexpression not only restored ER-mitochondria interactions and Ca2+ transfer but also rescued mitochondrial dysfunction. Our results describe a key role of NCS1 in ER-mitochondria cross-talk, uncover a pathogenic mechanism for Wolfram syndrome, and potentially reveal insights into the pathogenesis of other neurodegenerative diseases.

โ€ข Bioblast editor: Plangger M โ€ข O2k-Network Lab: FR Montpellier Fauconnier J


Labels: MiParea: Respiration  Pathology: Inherited, Neurodegenerative 

Organism: Human  Tissue;cell: Fibroblast  Preparation: Permeabilized cells  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex IV;cytochrome c oxidase  Regulation: Calcium, Ion;substrate transport  Coupling state: LEAK, OXPHOS  Pathway: N, S, NS  HRR: Oxygraph-2k 

Labels, 2018-11