Mitochondria are thus emerging as crucial players in the pathology of many different diseases, both as primary or secondary executioners.
Indeed, apart from the primary cause, that is frequently far away from mitochondria and even in the extracellular matrix (see below), many diseases show as final step a general Ca2+ deregulation that in turn causes mitochondrial Ca2+ overload and cell death through PTP opening and mitochondria swelling.
For instance, Gandhi and co-workers found impaired Ca2+ efflux from mitochondria through the Na+/Ca2+ exchanger in neurons lacking PINK1, a serine threonine kinase implicated in autosomal recessive early-onset parkinsonism. This led to increased Ca2+ uptake capacity, decreased membrane potential, and increased ROS production, all leading to early triggering of the PTP opening and concomitant neuronal death 
Blockade of this final process, no matter the original cause, is thus emerging as an effective therapeutic strategy also in vivo
. Indeed, genetic ablation or pharmacological inhibition of Cyp D, a main regulator of the PTP, has been shown to decrease the mitochondrial alterations and ameliorate the pathology both in the case of Collagen VI deficiency and in the Scgd−/− mouse, a model for severe dystrophia