Mitochondrial Ca2+ handling as a cell signaling hub: lessons from astrocyte function

• Published in: Essays in biochemistry Vol. 67; no. 1; p. 63
• Main Authors: Cabral-Costa, João Victor, Kowaltowski, Alicia J
• Format: Journal Article
• Language: English
• Published: England 03-03-2023
• Subjects: Astrocytes - metabolism; Calcium - metabolism; Calcium Signaling - physiology; Mitochondria - metabolism; Mitochondrial Membranes - metabolism; metabolism; astrocytes; NCLX; calcium signalling; mitochondria; MCU
• ISSN: 1744-1358
• DOI: 10.1042/EBC20220094

Astrocytes are a heterogenous population of macroglial cells spread throughout the central nervous system with diverse functions, expression signatures, and intricate morphologies. Their subcellular compartments contain a distinct range of mitochondria, with functional microdomains exhibiting widespread activities, such as controlling local metabolism and Ca2+ signaling. Ca2+ is an ion of utmost importance, both physiologically and pathologically, and participates in critical central nervous system processes, including synaptic plasticity, neuron-astrocyte integration, excitotoxicity, and mitochondrial physiology and metabolism. The mitochondrial Ca2+ handling system is formed by the mitochondrial Ca2+ uniporter complex (MCUc), which mediates Ca2+ influx, and the mitochondrial Na+/Ca2+ exchanger (NCLX), responsible for most mitochondrial Ca2+ efflux, as well as additional components, including the mitochondrial permeability transition pore (mtPTP). Over the last decades, mitochondrial Ca2+ handling has been shown to be key for brain homeostasis, acting centrally in physiopathological processes such as astrogliosis, astrocyte-neuron activity integration, energy metabolism control, and neurodegeneration. In this review, we discuss the current state of knowledge regarding the mitochondrial Ca2+ handling system molecular composition, highlighting its impact on astrocytic homeostasis.