Presynaptic Mitochondrial Volume and Packing Density Scale with Presynaptic Power Demand.

Autor:	Justs KA; Integrative Biology and Neuroscience Graduate Program, Florida Atlantic University, Jupiter, Florida 33458.; Jupiter Life Sciences Initiative, Florida Atlantic University, Jupiter, Florida 33458., Lu Z; Integrative Biology and Neuroscience Graduate Program, Florida Atlantic University, Jupiter, Florida 33458.; Jupiter Life Sciences Initiative, Florida Atlantic University, Jupiter, Florida 33458., Chouhan AK; Wellcome - MRC Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, United Kingdom., Borycz JA; Department of Psychology and Neuroscience, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada., Lu Z; Department of Psychology and Neuroscience, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada., Meinertzhagen IA; Department of Psychology and Neuroscience, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada., Macleod GT; Jupiter Life Sciences Initiative, Florida Atlantic University, Jupiter, Florida 33458 macleodg@fau.edu.; Wilkes Honors College, Florida Atlantic University, Jupiter, Florida 33458.; Brain Institute, Florida Atlantic University, Jupiter, Florida 33458.; Institute for Human Health and Disease Intervention (I-HEALTH), Florida Atlantic University, Jupiter, Florida 33458.
Jazyk:	angličtina
Zdroj:	The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2022 Feb 09; Vol. 42 (6), pp. 954-967. Date of Electronic Publication: 2021 Dec 14.
DOI:	10.1523/JNEUROSCI.1236-21.2021
Abstrakt:	Stable neural function requires an energy supply that can meet the intense episodic power demands of neuronal activity. Neurons have presumably optimized the volume of their bioenergetic machinery to ensure these power demands are met, but the relationship between presynaptic power demands and the volume available to the bioenergetic machinery has never been quantified. Here, we estimated the power demands of six motor nerve terminals in female Drosophila larvae through direct measurements of neurotransmitter release and Ca 2+ entry, and via theoretical estimates of Na + entry and power demands at rest. Electron microscopy revealed that terminals with the highest power demands contained the greatest volume of mitochondria, indicating that mitochondria are allocated according to presynaptic power demands. In addition, terminals with the greatest power demand-to-volume ratio (∼66 nmol·min -1 ·µl -1 ) harbor the largest mitochondria packed at the greatest density. If we assume sequential and complete oxidation of glucose by glycolysis and oxidative phosphorylation, then these mitochondria are required to produce ATP at a rate of 52 nmol·min -1 ·µl -1 at rest, rising to 963 during activity. Glycolysis would contribute ATP at 0.24 nmol·min -1 ·µl -1 of cytosol at rest, rising to 4.36 during activity. These data provide a quantitative framework for presynaptic bioenergetics in situ , and reveal that, beyond an immediate capacity to accelerate ATP output from glycolysis and oxidative phosphorylation, over longer time periods presynaptic terminals optimize mitochondrial volume and density to meet power demand. SIGNIFICANCE STATEMENT The remarkable energy demands of the brain are supported by the complete oxidation of its fuel but debate continues regarding a division of labor between glycolysis and oxidative phosphorylation across different cell types. Here, we exploit the neuromuscular synapse, a model for studying neurophysiology, to elucidate fundamental aspects of neuronal energy metabolism that ultimately constrain rates of neural processing. We quantified energy production rates required to sustain activity at individual nerve terminals and compared these with the volume capable of oxidative phosphorylation (mitochondria) and glycolysis (cytosol). We find strong support for oxidative phosphorylation playing a primary role in presynaptic terminals and provide the first in vivo estimates of energy production rates per unit volume of presynaptic mitochondria and cytosol. (Copyright © 2022 the authors.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu