Fig. 3

Mitochondrial damage is present in fibroblasts obtained from patients with NDs. Current evidence shows that skin fibroblasts display similar mitochondrial features as in neuronal cells, either in normal or pathological conditions. In non-pathological conditions, skin fibroblasts show healthy mitochondria highlighted by OXPHOS activity, high ATP production, calcium homeostasis, redox balance, and mitochondrial dynamics balance (a). Importantly, mitochondrial failure has been studied in brains of patients with NDs, and also reported in skin fibroblasts from ND patients. In this context, skin fibroblasts obtained from ND patients show mitochondrial swelling through mPTP opening, reduced ATP levels, oxidative stress, decreased antioxidant defenses, redox imbalance, mtDNA damage, and accumulation of fragmented mitochondria (b). These mitochondrial features are critical to synaptic function, and any abnormalities in these processes would contribute to neurodegeneration