The GTPase dMiro is required for axonal transport of mitochondria to Drosophila synapses.
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.
Guo
Xiufang
X
Arizona Research Laboratories, Division of Neurobiology, University of Arizona, Tucson, Arizona 85721, USA.
Macleod
Greg T
GT
Wellington
Andrea
A
Hu
Fangle
F
Panchumarthi
Sarvari
S
Schoenfield
Miriam
M
Marin
Leo
L
Charlton
Milton P
MP
Atwood
Harold L
HL
Zinsmaier
Konrad E
KE
D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D002522:Chlorocebus aethiops; D004330:Drosophila / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006706:Homeostasis; D007814:Larva; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D009043:Motor Activity / Q000502:physiology; D009046:Motor Neurons / Q000378:metabolism; D009132:Muscles / Q000648:ultrastructure; D009154:Mutation; D009411:Nerve Endings / Q000378:metabolism; D009469:Neuromuscular Junction / Q000502:physiology; D009474:Neurons / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000648:ultrastructure; D013569:Synapses / Q000502:physiology*; D022161:Transport Vesicles / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D029721:Drosophila Proteins; C504427:Miro protein, Drosophila; D020741:rho GTP-Binding Proteins; D002118:Calcium