title: Cytosolic calcium coordinates mitochondrial energy metabolism with presynaptic activity.
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.
authors.affiliation: Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
authors.forename: Amit K
authors.initials: AK
authors.lastname: Chouhan
authors.forename: Maxim V
authors.initials: MV
authors.lastname: Ivannikov
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Lu
authors.forename: Mutsuyuki
authors.initials: M
authors.lastname: Sugimori
authors.forename: Rodolfo R
authors.initials: RR
authors.lastname: Llinas
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Macleod
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002118:Calcium / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism*; D004330:Drosophila; D004734:Energy Metabolism / Q000502:physiology*; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008928:Mitochondria / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000502:physiology
chemical_list: D002118:Calcium