Miro1 Is a Calcium Sensor for Glutamate Receptor-Dependent Localization of Mitochondria at Synapses

By Andrew F. Macaskill, J. E. Rinholm, Alison E. Twelvetrees, I. Arancibia-Carcamo, J. Muir, Å. Fransson, P. Aspenstrom, David Attwell, J. Kittler. Neuron, 2009

692 citations recorded by the source corpus.

Summary Energy use, mainly to reverse ion movements in neurons, is a fundamental constraint on brain information processing. Trafficking of mitochondria to locations in neurons where there are large ion fluxes is essential for powering neural function. Mitochondrial trafficking is regulated by Ca2+ entry through ionotropic glutamate receptors, but the underlying mechanism is unknown. We show that the protein Miro1 links mitochondria to KIF5 motor proteins, allowing mitochondria to move along microtubules. This linkage is inhibited by micromolar levels of Ca2+ binding to Miro1. With the EF hand domains of Miro1 mutated to prevent Ca2+ binding, Miro1 could still facilitate mitochondrial motility, but mitochondrial stopping induced by glutamate or neuronal activity was blocked. Activating neuronal NMDA receptors with exogenous or synaptically released glutamate led to Miro1 positioning mitochondria at the postsynaptic side of synapses. Thus, Miro1 is a key determinant of how energy supply is matched to energy usage in neurons.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/f466c7f58aa2c24081f37e0ee401c5f72dfbae7d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

In Molecular Biology

Citations in the corpus

Kinesin superfamily motor proteins and intracellular transport (2009, background): “The other model suggests that high Ca 2+ disrupts the binding between KIF5 proteins and the Milton–Miro adaptor complex, although how the EF hand motif is involved remains unclea”
AXONAL TRANSPORT: CARGO-SPECIFIC MECHANISMS OF MOTILITY AND REGULATION (2014, background): “…2013; Fu et al., 2014); JIP3 regulates the injury-signaling pathway in mammalian cells (Cavalli et al., 2005) and lysosomal motility in zebrafish (Drerup and Nechiporuk, 2013); and the Miro/TRAK complex regulates motors bound to mitochondria (Macaskill et al., 2009b; Wang and Schwarz, 2009).”
Synaptic energy use and supply. (2012, positive): “Speculatively, therefore, a small [Ca2+]i rise may stop microtubule-based transport (MacAskill et al., 2009; Wang and Schwarz, 2009) and promote local actin-based transport, until the mitochondrion encounters a higher [Ca2+]i, which will stop actin-based transport.”
Mitochondria: In Sickness and in Health (2012, background): “Mitochondria: In Sickness and in Health”
Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration (2012, background): “Mitochondrial transport in neurons is regulated in response to acute application of glutamat”
Metabolic regulation of mitochondrial dynamics (2016, background): “Multiple mechanistic models have been proposed, but they all center on conformational changes triggered by calcium binding to Miro (Macaskill et al., 2009; Wang and Schwarz, 2009; Chen and Sheng, 2013).”