Ca2+ handling at the mitochondria-ER contact sites in neurodegeneration

Disruption of ER‐mitochondria tethering and signalling in C9orf72‐associated amyotrophic lateral sclerosis and frontotemporal dementia

“…IP3 receptor and VDAC1 thus represent a channel for delivery of Ca 2+ to mitochondria. IP3 receptors and VDAC1 are well‐characterised ER and mitochondrial proteins respectively (Csordas et al, 2018 ; Lim et al, 2021 ; Paillusson et al, 2016 ).…”

Uncontrolled mitochondrial calcium uptake underlies the pathogenesis of neurodegeneration in MICU1-deficient mice and patients

“…Neurons developed complex Ca 2+ signaling pathways that are engaged in the control of cellular metabolism, cell survival, gene expression, and membrane excitability. To induce a cytoplasmic [Ca 2+ ] ([Ca 2+ ] c ) rise, Ca 2+ enters neurons mainly through voltage-gated or ligand-activated Ca 2+ channels ( 21 ), and mobilized from the endoplasmic reticulum Ca 2+ store ( 22 ). Mitochondria take up Ca 2+ during the [Ca 2+ ] c signals and subsequently release Ca 2+ back to the cytoplasm.…”

Deletion of calcineurin from astrocytes reproduces proteome signature of Alzheimer's disease and epilepsy and predisposes to seizures

“…Disrupted intracellular Ca 2+ signalling, bioenergetic deficit and impairment of protein synthesis and degradation represent, perhaps, the most important features of early AD pathogenesis [31,32,33,34]. It has been suggested that alterations of inter-organellar communication, in particular of the ER-mitochondrial Ca 2+ transfer, may represent central event in AD cellular pathology [35,36,37,38]. We speculate that, in AD astrocytes, alterations of CaN activity may provide a link between deregulation of Ca 2+ homeostasis, bioenergetic deficit and cellular disproteostasis.…”