TY - JOUR
T1 - The GTPase dMiro is required for axonal transport of mitochondria to drosophila synapses
AU - Guo, Xiufang
AU - Macleod, Greg T.
AU - Wellington, Andrea
AU - Hu, Fangle
AU - Panchumarthi, Sarvari
AU - Schoenfield, Miriam
AU - Marin, Leo
AU - Charlton, Milton P.
AU - Atwood, Harold L.
AU - Zinsmaier, Konrad E.
N1 - Funding Information:
This study is dedicated to Konrad Zinsmaier, Sr. (1921-2004) for his invaluable support to K.E.Z. We thank Patty Jansma, Jinhui Zhang, and the University of Arizona DNA sequencing facility for their help. We thank Patrik Verstreken, Hugo Bellen, and Tom Schwarz, for critical comments and sharing unpublished information. We thank Bill Saxton, Tom Schwarz, Hugo Bellen, Mani Ramaswami, Erich Buchner, and Alan Nighorn for fly strains or antibodies. We thank Joanne Pearce for early contributions and Gurbir Sekhon for help with the 3-D reconstruction. G.S. was supported by a Summer Research Studentship from the Natural Sciences and Engineering Research Council of Canada. M.S. was supported by an REU Award (NSF) through the Undergraduate Biology Research Program of the University of Arizona. This study was supported by grants to K.E.Z. (National Science Foundation) and to H.L.A. (Natural Sciences and Engineering Research Council of Canada).
PY - 2005/8/4
Y1 - 2005/8/4
N2 - We have identified EMS-induced mutations in Drosophila Miro (dMiro), an atypical mitochondrial GTPase that is orthologous to human Miro (hMiro). Mutant dmiro animals exhibit defects in locomotion and die prematurely. Mitochondria in dmiro mutant muscles and neurons are abnormally distributed. Instead of being transported into axons and dendrites, mitochondria accumulate in parallel rows in neuronal somata. Mutant neuromuscular junctions (NMJs) lack presynaptic mitochondria, but neurotransmitter release and acute Ca2+ buffering is only impaired during prolonged stimulation. Neuronal, but not muscular, expression of dMiro in dmiro mutants restored viability, transport of mitochondria to NMJs, the structure of synaptic boutons, the organization of presynaptic microtubules, and the size of postsynaptic muscles. In addition, gain of dMiro function causes an abnormal accumulation of mitochondria in distal synaptic boutons of NMJs. Together, our findings suggest that dMiro is required for controlling anterograde transport of mitochondria and their proper distribution within nerve terminals.
AB - We have identified EMS-induced mutations in Drosophila Miro (dMiro), an atypical mitochondrial GTPase that is orthologous to human Miro (hMiro). Mutant dmiro animals exhibit defects in locomotion and die prematurely. Mitochondria in dmiro mutant muscles and neurons are abnormally distributed. Instead of being transported into axons and dendrites, mitochondria accumulate in parallel rows in neuronal somata. Mutant neuromuscular junctions (NMJs) lack presynaptic mitochondria, but neurotransmitter release and acute Ca2+ buffering is only impaired during prolonged stimulation. Neuronal, but not muscular, expression of dMiro in dmiro mutants restored viability, transport of mitochondria to NMJs, the structure of synaptic boutons, the organization of presynaptic microtubules, and the size of postsynaptic muscles. In addition, gain of dMiro function causes an abnormal accumulation of mitochondria in distal synaptic boutons of NMJs. Together, our findings suggest that dMiro is required for controlling anterograde transport of mitochondria and their proper distribution within nerve terminals.
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U2 - 10.1016/j.neuron.2005.06.027
DO - 10.1016/j.neuron.2005.06.027
M3 - Article
C2 - 16055062
AN - SCOPUS:23044432581
SN - 0896-6273
VL - 47
SP - 379
EP - 393
JO - Neuron
JF - Neuron
IS - 3
ER -