Leading science, pioneering therapies
CRM Publications

Cytosolic calcium coordinates mitochondrial energy metabolism with presynaptic activity.

TitleCytosolic calcium coordinates mitochondrial energy metabolism with presynaptic activity.
Publication TypeJournal Article
Year of Publication2012
AuthorsChouhan AK, Ivannikov MV, Lu Z, Sugimori M, Llinas RR, Macleod GT
JournalJ Neurosci
Volume32
Issue4
Pagination1233-43
Date Published2012 Jan 25
ISSN1529-2401
KeywordsAnimals, Animals, Genetically Modified, Calcium, Cytosol, Drosophila, Energy Metabolism, Membrane Potential, Mitochondrial, Mitochondria, Presynaptic Terminals
Abstract

Most neurons fire in bursts, imposing episodic energy demands, but how these demands are coordinated with oxidative phosphorylation is still unknown. Here, using fluorescence imaging techniques on presynaptic termini of Drosophila motor neurons (MNs), we show that mitochondrial matrix pH (pHm), inner membrane potential (Δψm), and NAD(P)H levels ([NAD(P)H]m) increase within seconds of nerve stimulation. The elevations of pHm, Δψm, and [NAD(P)H]m indicate an increased capacity for ATP production. Elevations in pHm were blocked by manipulations that blocked mitochondrial Ca2+ uptake, including replacement of extracellular Ca2+ with Sr2+ and application of either tetraphenylphosphonium chloride or KB-R7943, indicating that it is Ca2+ that stimulates presynaptic mitochondrial energy metabolism. To place this phenomenon within the context of endogenous neuronal activity, the firing rates of a number of individually identified MNs were determined during fictive locomotion. Surprisingly, although endogenous firing rates are significantly different, there was little difference in presynaptic cytosolic Ca2+ levels ([Ca2+]c) between MNs when each fires at its endogenous rate. The average [Ca2+]c level (329±11 nM) was slightly above the average Ca2+ affinity of the mitochondria (281±13 nM). In summary, we show that when MNs fire at endogenous rates, [Ca2+]c is driven into a range where mitochondria rapidly acquire Ca2+. As we also show that Ca2+ stimulates presynaptic mitochondrial energy metabolism, we conclude that [Ca2+]c levels play an integral role in coordinating mitochondrial energy metabolism with presynaptic activity in Drosophila MNs.

DOI10.1523/JNEUROSCI.1301-11.2012
Alternate JournalJ. Neurosci.
PubMed ID22279208
PubMed Central IDPMC3531998
Grant ListR01 NS061914 / NS / NINDS NIH HHS / United States
R01 NS061914-03 / NS / NINDS NIH HHS / United States
Publication institute
Other