Impaired Ca2+ signaling indicates disturbed mitochondrial function in fibroblasts from patients with sporadic and familial ALS

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive, devastating, neurodegenerative disorder affecting upper and lower motor neurons. Common mechanisms of ALS pathogenesis disturb cellular calcium homeostasis and cause mitochondrial dysfunction. Both influence mutually each other. As a result, chronic mitochondrial energy stress impairs cellular signaling and transport processes, leading to degeneration of motor neurons. We measured cytosolic Ca²⁺ in healthy and ALS fibroblasts. Mitochondrial calcium retention capacity in fibroblasts obtained from patients with sporadic (sALS) and familial (fALS) ALS differed between two subtypes and from healthy individuals. Changes of [Ca²⁺]_cyt dynamics in ALS fibroblasts was partially rescued by treatment with antioxidants (Trolox and CoQ₁₀). These results confirm a causative role of oxidative stress in mitochondrial dysfunction linked to ALS.

Cite:

Gainutdinov T, Debska-Vielhaber G, Gizatullina Z, Vielhaber S, Orynbayeva Z, Gellerich FN (2022) Impaired Ca²⁺ signaling indicates disturbed mitochondrial function in fibroblasts from patients with sporadic and familial ALS. Bioenerg Commun 2022.18. https://doi.org/10.26124/bec:2022-0018