Mitochondrial calcium signalling and neurodegenerative diseases

Elena Britti, Fabien Delaspre, Jordi Tamarit, Joaquim Ros; Neuronal Signaling Dec 2018, 2 (4) NS20180061; DOI: 10.1042/NS20180061

Mitochondrial calcium homoeostasis clearly contributes to cellular fitness and survival. Maintenance of accurate calcium levels is highly regulated by mitochondrial proteins that are connected, either directly or via other proteins, to ER calcium stores. As described in this review, prior to cell death, mitochondrial calcium deregulation could be the consequence of increased influx (MCU complex), or decreased efflux (Na+/Ca2+ exchanger) or altered capacity for calcium buffering caused by mitochondrial damage, such as MPTP opening. Calcium deregulation would then lead to several neurodegenerative processes that resulted in cell death. Thus, identifying specific targets to maintain calcium balance and mitochondrial function appears to be of paramount importance in preventing, alleviating or even curing neurodegenerative diseases.
Although the initial steps of the process through which decreased levels of frataxin leads to neurodegeneration are still unknown, the above-reported findings clearly point to an important role of calcium deregulation in the pathophysiology of FA. Therapeutic strategies that impact on the proteins responsible for calcium overload and its consequences could be of great value for developing a cure for the disease.