Exploring the contribution of the mitochondrial disulfide relay system to Parkinson's disease: the PINK1/CHCHD4 interplay.

Parkinson’s disease (PD) is a common movement disorder of the elderly caused by the degeneration of dopaminergic neurons in the substantia nigra pars compacta of the brain.
Both environmental and genetic factors pointed out mitochondrial dysfunction as a major cause of neurodegeneration in PD. Pioneering studies using mitochondrial toxins revealed their ability to trigger dopaminergic cell death and irreversible parkinsonism in different animal models (Poewe et al., 2017). Typical features of mitochondrial dysfunction have been also observed in the human brain of idiopathic PD cases, showing alterations of respiratory chain complex I and IV activity, accumulation of mtDNA deletions and increased oxidative stress (Bender et al., 2006). Moreover, a number of genes found mutated in familial PD forms encode for proteins involved in the maintenance of mitochondrial homeostasis and quality control. Among these, the PINK1 gene encodes a mitochondrial serine/threonine kinase implicated in key neuroprotective functions, including mitophagy, regulation of mitochondrial transport, control of the mitochondria/endoplasmic reticulum crosstalk and calcium homeostasis (Brunelli et al., 2020).