Context-Dependent modulation of astrocytic Ca2+ signals by mitochondria: a computational study
- 1Department of Physics, School of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo, Bandeirantes avenue, Ribeirão Preto, 14040-900 São Paulo Brazil
Abstract
Mitochondria regulate intracellular Ca2+ by uptake through the mitochondrial Ca2+ uniporter (MCU) and release via the mitochondrial permeability transition pore (mPTP). In astrocytes, neurotransmitter stimulation evokes Ca2+ signaling, yet the role of mitochondria in shaping these responses remains unclear. We extended a compartmental astrocyte model developed by our group to include MCU- and mPTP-mediated dynamics, and simulated glutamatergic and dopaminergic inputs modeled as Poisson processes driving IP3 synthesis through the phospholipase-C (PLC) pathway. Both unipolar and bifurcated-terminal morphologies were considered, with mitochondria positioned in alternating compartments starting from the soma; distal compartments contained mitochondria only when sufficiently large. Simulations show that mitochondria modulate Ca2+ signaling in a context-dependent manner: under weak glutamatergic input, they reduce oscillation frequency and limit signal propagation, whereas under strong glutamatergic input or dopaminergic modulation, they enhance Ca2+ responses by reducing Ca2+-dependent IP3 degradation. These results suggest that mitochondria can play an important role in shaping the spatial organization of Ca2+ signaling in astrocytes.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s10827-026-00956-3.
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BibTeX
@article{bezerra2026contextdependent,
title = {{Context-Dependent modulation of astrocytic Ca2+ signals by mitochondria: a computational study}},
author = {Thiago Ohno Bezerra and Antonio C. Roque},
journal = {Journal of Computational Neuroscience},
year = {2026},
month = sep,
doi = {10.1007/s10827-026-00956-3},
url = {https://doi.org/10.1007/s10827-026-00956-3},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Context-Dependent modulation of astrocytic Ca2+ signals by mitochondria: a computational study
AU - Thiago Ohno Bezerra
AU - Antonio C. Roque
PY - 2026
DA - 2026/09/25
JO - Journal of Computational Neuroscience
DO - 10.1007/s10827-026-00956-3
UR - https://doi.org/10.1007/s10827-026-00956-3
AB - Mitochondria regulate intracellular Ca2+ by uptake through the mitochondrial Ca2+ uniporter (MCU) and release via the mitochondrial permeability transition pore (mPTP). In astrocytes, neurotransmitter stimulation evokes Ca2+ signaling, yet the role of mitochondria in shaping these responses remains unclear. We extended a compartmental astrocyte model developed by our group to include MCU- and mPTP-mediated dynamics, and simulated glutamatergic and dopaminergic inputs modeled as Poisson processes driving IP3 synthesis through the phospholipase-C (PLC) pathway. Both unipolar and bifurcated-terminal morphologies were considered, with mitochondria positioned in alternating compartments starting from the soma; distal compartments contained mitochondria only when sufficiently large. Simulations show that mitochondria modulate Ca2+ signaling in a context-dependent manner: under weak glutamatergic input, they reduce oscillation frequency and limit signal propagation, whereas under strong glutamatergic input or dopaminergic modulation, they enhance Ca2+ responses by reducing Ca2+-dependent IP3 degradation. These results suggest that mitochondria can play an important role in shaping the spatial organization of Ca2+ signaling in astrocytes. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s10827-026-00956-3.
SN - 0929-5313
SN - 1573-6873
ER -