Abstract
Uptake of Ca2+ into the mitochondrial matrix controls cellular metabolism and survival-death pathways. Several genes are implicated in controlling mitochondrial Ca2+ uptake (mitochondrial calcium regulatory genes, MCRGs), however, less is known about the factors which influence their expression level. Here we have compared MCRG mRNA expression, in neural cells of differing type (cortical neurons vs. astrocytes), differing neuronal subtype (CA3 vs. CA1 hippocampus) and in response to Ca2+ influx, using a combination of qPCR and RNA-seq analysis. Of note, we find that the Mcu-regulating Micu gene family profile differs substantially between neurons and astrocytes, while expression of Mcu itself is markedly different between CA3 and CA1 regions in the adult hippocampus. Moreover, dynamic control of MCRG mRNA expression in response to membrane depolarization-induced Ca2+ influx is also apparent, resulting in repression of Letm1, as well as Mcu. Thus, the mRNA expression profile of MCRGs is not fixed, which may cause differences in the coupling between cytoplasmic and mitochondrial Ca2+, as well as diversity of mitochondrial Ca2+ uptake mechanisms.
Highlights
Energized mitochondria are capable of taking up Ca2+ across the inner mitochondrial membrane into their matrix [1, 2]
Whether transcription of other mitochondrial calcium regulatory genes (MCRGs) is influenced by Ca2+ signals is unclear. It is not well understood how the basal expression profile of MCRGs varies with cell type. We have investigated these issues in the current study, focussing on neural cells, since mitochondrial Ca2+ overload is implicated in excitotoxic neuronal death, and physiological uptake into mitochondria thought to play a role in neuronal adaptive energy production in response to electrical activity [4]
Cortical Astrocytes and Neurons Differ in Their MCRG mRNA Expression Profile
Summary
Energized mitochondria are capable of taking up Ca2+ across the inner mitochondrial membrane into their matrix [1, 2]. This Ca2+ uptake has the capacity to modulate and buffer cytoplasmic Ca2+ signals, and is thought to regulate several metabolic pathways within the mitochondria itself [3, 4]. Many genes involved in Ca2+ influx and efflux across the inner mitochondrial membrane have been discovered and added to more established candidates [1, 2, 9]. The gene encoding the pore-forming component of the potential-driven mitochondrial calcium.
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