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

Biomolecules

Marcella Vacca¹  Alessandra Palazzi¹  Yi-Shin Lee¹  Francesco Filippini²  Matteo Gasparotto² 

[1] Institute of Genetics and Biophysics “A. Buzzati Traverso”, CNR, Via Pietro Castellino, 111, 80131 Naples, Italy;Synthetic Biology and Biotechnology Unit, Department of Biology, University of Padua, Via Ugo Bassi 58/B, 35131 Padua, Italy;

关键词: mitochondria;    chromatin remodeling;    subcellular trafficking;    autophagy;    mitophagy;    MeCP2;   

DOI  :  10.3390/biom12050625

来源: DOAJ

【 摘 要 】

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

【 授权许可】

Unknown