Ca

From PubMed via Jisc Publications RouterHistory: received 2021-07-07, revised 2021-08-03, accepted 2021-08-03Publication status: aheadofprintMitochondria-endoplasmic reticulum (ER) contact sites (MERCS) are morpho-functional units, formed at the loci of close apposition of the ER-forming endomembrane and outer mitochondrial membrane (OMM). These sites contribute to fundamental cellular processes including lipid biosynthesis, autophagy, apoptosis, ER-stress and calcium (Ca ) signalling. At MERCS, Ca ions are transferred from the ER directly to mitochondria through a core protein complex composed of inositol-1,4,5 trisphosphate receptor (InsP R), voltage-gated anion channel 1 (VDAC1), mitochondrial calcium uniporter (MCU) and adaptor protein glucose-regulated protein 75 (Grp75); this complex is regulated by several associated proteins. Deregulation of ER-mitochondria Ca transfer contributes to pathogenesis of neurodegenerative and other diseases. The efficacy of Ca transfer between ER and mitochondria depends on the protein composition of MERCS, which controls ER-mitochondria interaction regulating, for example, the transversal distance between ER membrane and OMM and the extension of the longitudinal interface between ER and mitochondria. These parameters are altered in neurodegeneration. Here we overview the ER and mitochondrial Ca homeostasis, the composition of ER-mitochondrial Ca transfer machinery and alterations of the ER-mitochondria Ca transfer in three major neurodegenerative diseases: motor neurone diseases, Parkinson disease and Alzheimer's disease. [Abstract copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.