Mitochondrial phosphagen kinases support the volatile power demands of motor nerve terminals.

Autor: Justs KA; Integrative Biology and Neuroscience Graduate Program, Florida Atlantic University, Jupiter, FL, USA., Sempertegui S; Department of Physics, College of Science, Florida Atlantic University, Boca Raton, FL, USA., Riboul DV; Integrative Biology and Neuroscience Graduate Program, Florida Atlantic University, Jupiter, FL, USA., Oliva CD; Wilkes Honors College, Florida Atlantic University, Jupiter, FL, USA., Durbin RJ; Department of Physiology and Cell Biology, Reno School of Medicine, University of Nevada, Reno, NV, USA., Crill S; Wilkes Honors College, Florida Atlantic University, Jupiter, FL, USA., Stawarski M; Wilkes Honors College, Florida Atlantic University, Jupiter, FL, USA., Su C; Wilkes Honors College, Florida Atlantic University, Jupiter, FL, USA., Renden RB; Department of Physiology and Cell Biology, Reno School of Medicine, University of Nevada, Reno, NV, USA., Fily Y; Wilkes Honors College, Florida Atlantic University, Jupiter, FL, USA., Macleod GT; Wilkes Honors College, Florida Atlantic University, Jupiter, FL, USA.; Institute for Human Health & Disease Intervention, Florida Atlantic University, Jupiter, FL, USA.; Stiles-Nicholson Brain Institute, Florida Atlantic University, Jupiter, FL, USA.
Jazyk: angličtina
Zdroj: The Journal of physiology [J Physiol] 2023 Dec; Vol. 601 (24), pp. 5705-5732. Date of Electronic Publication: 2023 Nov 09.
DOI: 10.1113/JP284872
Abstrakt: Motor neurons are the longest neurons in the body, with axon terminals separated from the soma by as much as a meter. These terminals are largely autonomous with regard to their bioenergetic metabolism and must burn energy at a high rate to sustain muscle contraction. Here, through computer simulation and drawing on previously published empirical data, we determined that motor neuron terminals in Drosophila larvae experience highly volatile power demands. It might not be surprising then, that we discovered the mitochondria in the motor neuron terminals of both Drosophila and mice to be heavily decorated with phosphagen kinases - a key element in an energy storage and buffering system well-characterized in fast-twitch muscle fibres. Knockdown of arginine kinase 1 (ArgK1) in Drosophila larval motor neurons led to several bioenergetic deficits, including mitochondrial matrix acidification and a faster decline in the cytosol ATP to ADP ratio during axon burst firing. KEY POINTS: Neurons commonly fire in bursts imposing highly volatile demands on the bioenergetic machinery that generates ATP. Using a computational approach, we built profiles of presynaptic power demand at the level of single action potentials, as well as the transition from rest to sustained activity. Phosphagen systems are known to buffer ATP levels in muscles and we demonstrate that phosphagen kinases, which support such phosphagen systems, also localize to mitochondria in motor nerve terminals of fruit flies and mice. By knocking down phosphagen kinases in fruit fly motor nerve terminals, and using fluorescent reporters of the ATP:ADP ratio, lactate, pH and Ca 2+ , we demonstrate a role for phosphagen kinases in stabilizing presynaptic ATP levels. These data indicate that the maintenance of phosphagen systems in motor neurons, and not just muscle, could be a beneficial initiative in sustaining musculoskeletal health and performance.
(© 2023 The Authors. The Journal of Physiology © 2023 The Physiological Society.)
Databáze: MEDLINE
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