Nuclear and Cytoplasmatic Players in Mitochondria-Related CNS Disorders: Chromatin Modifications and Subcellular Trafficking

Aberrant mitochondrial phenotypes are common to many central nervous system (CNS)disorders, including neurodegenerative and neurodevelopmental diseases. Mitochondrial functionand homeostasis depend on proper control of several biological processes such as chromatin remodelingand transcriptional control, post-transcriptional events, vesicle and organelle subcellulartrafficking, fusion, and morphogenesis. Mutation or impaired regulation of major players that orchestratesuch processes can disrupt cellular and mitochondrial dynamics, contributing to neurologicaldisorders. The first part of this review provides an overview of a functional relationship betweenchromatin players and mitochondria. Specifically, we relied on specific monogenic CNS disorderswhich share features with mitochondrial diseases. On the other hand, subcellular trafficking is coordinateddirectly or indirectly through evolutionarily conserved domains and proteins that regulatethe dynamics of membrane compartments and organelles, including mitochondria. Among these"building blocks", longin domains and small GTPases are involved in autophagy and mitophagy, cellreshaping, and organelle fusion. Impairments in those processes significantly impact CNS as welland are discussed in the second part of the review. Hopefully, in filling the functional gap betweenthe nucleus and cytoplasmic organelles new routes for therapy could be disclosed.