CMBN PhD student publishes in Neuron on a novel mechanism targeting mitochondria to generate ATP at synapses

Johanne Egge Rinholm, a PhD student working with Linda H Bergersen, and collaborating with the groups of David Attwell and Josef Kittler in University College London, has co-authored a paper in Neuron demonstrating how mitochondria are targeted to the postsynaptic side of synapses.

Our brains cannot function without energy, which is supplied as glucose and oxygen in the blood. Most of the brain’s energy supply is used to pump back out of neurons the ions that enter to generate action potentials and synaptic potentials. Any deficiency of the energy supply, as occurs in stroke and after spinal cord injury, leads to nerve cell damage and thus causes mental and physical disability.

Because nerve cells are so large they need special mechanisms to locate mitochondria at spatial locations where the energy is needed. Synapses are sites of particularly large energy consumption. The new paper has revealed a key mechanism which locates mitochondria at synapses.

Mitochondria can be moved around cells by kinesin motors on intracellular microtubule tracks (for a movie visit http://www.ucl.ac.uk/npp/jk.html and look at the bottom of the page). The new research discovered that the linkage of mitochondria to these motors is mediated by a protein called Miro. Importantly, this linkage is uncoupled by calcium ions, which enter through NMDA receptors when synapses are activated. The resulting uncoupling of mitochondria from their motors leads to them being "parked" near the active synapses where they are needed to generate energy.

This work advances our understanding of how neurons are powered. It also explains why in pathological conditions like stroke, which dramatically raise the internal calcium concentration in nerve cells, all movements of mitochondria within the cell halt.

MacAskill AF, Rinholm JE, Twelvetrees AE, Arancibia-Carcamo IL, Muir J, Fransson A, Aspenstrom P, Attwell D, Kittler JT (2009)
Miro1 is a calcium sensor for glutamate receptor-dependent localization of mitochondria at synapses
Neuron 61, 541-555

Related News and Views:
Cai Q, Sheng Z-H (2009)
Moving or stopping mitochondria: Miro as a traffic cop by sensing calcium
Neuron 61, 493-496

Contact details for further information:
Johanne E Rinholm, +47 907 68 382, j.e.rinholm@medisin.uio.no
Josef Kittler, +44 20 7679 3218, j.kittler@ucl.ac.uk