Transient Opening of the Mitochondrial Permeability Transition Pore Induces Microdomain Calcium Transients in Astrocyte Processes

Amit Agarwal, Pei Hsun Wu, Ethan G. Hughes, Masahiro Fukaya, Max A. Tischfield, Abraham J. Langseth, Denis Wirtz, Dwight E. Bergles

Research output: Contribution to journalArticle

Abstract

Astrocytes extend highly branched processes that form functionally isolated microdomains, facilitating local homeostasis by redistributing ions, removing neurotransmitters, and releasing factors to influence blood flow and neuronal activity. Microdomains exhibit spontaneous increases in calcium (Ca2+), but the mechanisms and functional significance of this localized signaling are unknown. By developing conditional, membrane-anchored GCaMP3 mice, we found that microdomain activity that occurs in the absence of inositol triphosphate (IP3)-dependent release from endoplasmic reticulum arises through Ca2+ efflux from mitochondria during brief openings of the mitochondrial permeability transition pore. These microdomain Ca2+ transients were facilitated by the production of reactive oxygen species during oxidative phosphorylation and were enhanced by expression of a mutant form of superoxide dismutase 1 (SOD1 G93A) that causes astrocyte dysfunction and neurodegeneration in amyotrophic lateral sclerosis (ALS). By localizing mitochondria to microdomains, astrocytes ensure local metabolic support for energetically demanding processes and enable coupling between metabolic demand and Ca2+ signaling events.

LanguageEnglish (US)
Pages587-605.e7
JournalNeuron
Volume93
Issue number3
DOIs
StatePublished - Feb 8 2017

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Astrocytes
Calcium
Mitochondria
Oxidative Phosphorylation
Amyotrophic Lateral Sclerosis
Inositol
Endoplasmic Reticulum
Neurotransmitter Agents
Reactive Oxygen Species
Homeostasis
Ions
Membranes
mitochondrial permeability transition pore
Superoxide Dismutase-1
triphosphoric acid

Keywords

  • astrocyte
  • ATP
  • calcium
  • cortex
  • in vivo
  • metabolism
  • microdomain
  • mitochondria
  • two-photon

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Transient Opening of the Mitochondrial Permeability Transition Pore Induces Microdomain Calcium Transients in Astrocyte Processes. / Agarwal, Amit; Wu, Pei Hsun; Hughes, Ethan G.; Fukaya, Masahiro; Tischfield, Max A.; Langseth, Abraham J.; Wirtz, Denis; Bergles, Dwight E.

In: Neuron, Vol. 93, No. 3, 08.02.2017, p. 587-605.e7.

Research output: Contribution to journalArticle

Agarwal A, Wu PH, Hughes EG, Fukaya M, Tischfield MA, Langseth AJ et al. Transient Opening of the Mitochondrial Permeability Transition Pore Induces Microdomain Calcium Transients in Astrocyte Processes. Neuron. 2017 Feb 8;93(3):587-605.e7. Available from, DOI: 10.1016/j.neuron.2016.12.034
Agarwal, Amit ; Wu, Pei Hsun ; Hughes, Ethan G. ; Fukaya, Masahiro ; Tischfield, Max A. ; Langseth, Abraham J. ; Wirtz, Denis ; Bergles, Dwight E./ Transient Opening of the Mitochondrial Permeability Transition Pore Induces Microdomain Calcium Transients in Astrocyte Processes. In: Neuron. 2017 ; Vol. 93, No. 3. pp. 587-605.e7
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