A Ca2+-Dependent Mechanism Boosting Glycolysis and OXPHOS by Activating Aralar-Malate-Aspartate Shuttle, upon Neuronal Stimulation

• DOI: 10.1523/jneurosci.1463-21.2022
• Publication Date: 2022-05-11T03:30:13Z
• Authors: Irene Pérez-Liébana; Inés Juaristi; Paloma González-S...; Luis González-Moreno; Eduardo Rial; Maša Podunavac; Armen Zakarian; Jordi Molgó; Ainara Vallejo-Il...; Laura Mosqueira-M...; Adolfo Lopez de M...; Beatriz Pardo; Jorgina Satrústegui; Araceli del Arco
• Keywords: Uniporter; Bioenergetics; Anaerobic glycolysis

Calcium is an important second messenger regulating a bioenergetic response to the workloads triggered by neuronal activation. In embryonic mouse cortical neurons using glucose as only fuel, activation NMDA elicits strong workload (ATP demand)-dependent on Na + and Ca 2+ entry, stimulates uptake, glycolysis, pyruvate lactate production, oxidative phosphorylation (OXPHOS) in -dependent way. We find that upregulation of levels, respiration, but not all depend Aralar/AGC1/Slc25a12, mitochondrial aspartate-glutamate carrier, component malate-aspartate shuttle (MAS). MAS increases process inhibited presence BAPTA-AM, suggesting binding motifs Aralar may be involved Mitochondrial calcium uniporter (MCU) silencing had no effect, indicating none these processes required MCU-dependent uptake. The respiratory carbachol was also dependent Aralar, MCU. are endowed with constitutive ER-to-mitochondria flow maintaining basal cell bioenergetics which ryanodine receptors, RyR2, rather than InsP 3 R, responsible for release, MCU does participate. results reveal that, glucose, participate OXPHOS regulation under or stimulated conditions, while Aralar-MAS appears major pathway tuning simultaneously glycolysis SIGNIFICANCE STATEMENT Neuronal restore ion gradients altered matching increased ATP mechanisms still unknown. respiration way, independently effects inducer. play relevant role production oxygen consumption both unchanged silenced neurons. However, stimulation blunt absence -binding carrier Malate-Aspartate Shuttle suggest -regulated upregulates fuels through cytosolic NAD /NADH ratio.