Mitochondrial Alarmins Released by Degenerating Motor Axon Terminals
Mitochondrial alarmins released by degenerating PNAS PLUS motor axon terminals activate perisynaptic Schwann cells Elisa Duregottia, Samuele Negroa, Michele Scorzetoa, Irene Zornettaa, Bryan C. Dickinsonb,c,1, Christopher J. Changb,c, Cesare Montecuccoa,d,2, and Michela Rigonia,2 aDepartment of Biomedical Sciences, University of Padua, Padua 35131, Italy; bDepartment of Chemistry and Molecular and Cell Biology and cHoward Hughes Medical Institute, University of California, Berkeley, CA 94720; and dItalian National Research Council Institute of Neuroscience, Padua 35131, Italy Edited by Thomas C. Südhof, Stanford University School of Medicine, Stanford, CA, and approved December 22, 2014 (received for review September 5, 2014) An acute and highly reproducible motor axon terminal degeneration of nerve terminal degeneration (21). Indeed, these neurotoxins followed by complete regeneration is induced by some animal cause activation of the calcium-activated calpains that contribute to presynaptic neurotoxins, representing an appropriate and controlled cytoskeleton fragmentation (22). system to dissect the molecular mechanisms underlying degeneration Although clearly documented (4, 5, 20), the regeneration of and regeneration of peripheral nerve terminals. We have previously the motor axon terminals after presynaptic neurotoxins injection shown that nerve terminals exposed to spider or snake presynaptic is poorly known in its cellular and molecular aspects. Available neurotoxins degenerate as a result of calcium overload and mito- evidence indicates that, in general, regeneration of mechan- chondrial failure. Here we show that toxin-treated primary neurons ically damaged motor neuron terminals relies on all three cel- release signaling molecules derived from mitochondria: hydrogen lular components of the neuromuscular junction (NMJ): the peroxide, mitochondrial DNA, and cytochrome c.
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