Mitochondria-Endoplasmic Reticulum Interaction in Central Neurons

Abstract

The proteins presenilin-1/2 play a key role in the interactions between mitochondria and the endoplasmic reticulum at synaptic contacts of central neurons. Several novel observations suggest that mutations in presenilin-1 lead to an abnormal energy state, an early sign of neurodegeneration and Alzheimer’s disease. Recent studies suggest that in the postsynaptic region, calcium stores are widely represented in the spine apparatus, which is located in a strategically important compartment - the neck of mature mushroom-shaped dendritic spines. Moreover, in the dendritic shaft area, at the base of the spines, one finds oblong mitochondrial clusters supplying the postsynaptic area and the local protein synthesis with ATP. Calcium signals, generated by the postsynaptic membranes, affect both calcium release from local stores through ryanodine channels and the uptake based on store-operated calcium entry. The entire complex of nanoscale signaling most likely determines the production of ATP. Violation of the functional relationship between mitochondria and reticular calcium depots can lead to disruption of signaling pathways that stimulate ATP production at the stages of increased activity of individual synapses. In this chapter, we will present the signaling mechanisms of interaction between mitochondria, spine clusters, and calcium nano-stores in postsynaptic area.

Differential Role of Active Compounds in Mitophagy and Related Neurodegenerative Diseases

“…In dendrites, mitochondria are located at the base of the most functionally loaded dendritic spines, where they are responsible for providing energy for the main stages of synaptic plasticity: phosphorylation, externalization and synaptic recruitment of receptors, and changes in the structure of the dendritic spine. The quality of the mitochondrial state at the base of the dendritic spine, including membrane potential, also determines Ca 2+ homeostasis, its global and local gradients [ 1 , 2 , 29 ]. In astrocytic processes, mitochondria support the operation of glutamate transporter-1 (GLT-1), excitatory amino acid transporter (EAAT) 1 and 2, as well as many other functions [ 30 , 31 , 32 ].…”

“…The number of processes that depend on mitochondria in synapse is equal to all currently known molecular mechanisms in this area and requires a separate review. We have previously reported in more detail on the role of mitochondria in this area [ 1 ]. Thus, a functional deficiency of synaptic mitochondria leads to negative changes in this area ( Figure 1 ).…”

“…A normally functioning neuron and synapse are possible only in the presence of healthy mitochondria. In the synapse, mitochondria play the role not only of an energy station, but also as a calcium (Ca 2+ ) regulator and an inducer of apoptosis [ 1 , 2 ].…”

Presenilins and mitochondria—an intriguing link: mini-review

“…This, in turn, leads to a diminished ability to form stable synapses. Conversely, excessive levels of calcium transferred from the ER to mitochondria-associated ER membranes can give rise to mitochondrial Ca 2+ overload, leading to the decoupling of the oxidative phosphorylation chain and subsequent reduction in ATP production (Kushnireva and Korkotian, 2022). Strikingly, some studies report that mitochondrial Ca 2+ uptake in FAD-linked PS2 mutants is reduced as a result of decreased ER Ca 2+ , causing a blunted increase in cytosolic Ca 2+ after stimulation (Rossini et al, 2021).…”

SOCE as a regulator of neuronal activity

“…the IP 3 receptor) close to the target. This is the case for channels at the PM of neurons and astrocytes such as the Ca 2+ ‐activated chloride channel ANO1 (Jin et al., 2013; Jin et al., 2016) and the Ca 2+ ‐activated potassium channels BK (Shah et al., 2021; Weaver et al., 2007) as well as the mitochondria (Kushnireva & Korkotian, 2022). Another key element in the tunnelling mechanism is the central role played by the SERCA pump that contributes to restriction of the SOCE microdomain and refilling of the ER stores (Courjaret & Machaca, 2014; Courjaret & Machaca, 2020; Courjaret et al., 2018; Petersen et al., 2017).…”