Abstract
In eukaryotic cells, mitochondria form a dynamic interconnected network to respond to changing needs at different subcellular locations. A fundamental yet unanswered question regarding this network is whether, and if so how, local fusion and fission of individual mitochondria affect their global distribution. To address this question, we developed high-resolution computational image analysis techniques to examine the relations between mitochondrial fusion/fission and spatial distribution within the axon of Drosophila larval neurons. We found that stationary and moving mitochondria underwent fusion and fission regularly but followed different spatial distribution patterns and exhibited different morphology. Disruption of inner membrane fusion by knockdown of dOpa1, Drosophila Optic Atrophy 1, not only increased the spatial density of stationary and moving mitochondria but also changed their spatial distributions and morphology differentially. Knockdown of dOpa1 also impaired axonal transport of mitochondria. But the changed spatial distributions of mitochondria resulted primarily from disruption of inner membrane fusion because knockdown of Milton, a mitochondrial kinesin-1 adapter, caused similar transport velocity impairment but different spatial distributions. Together, our data reveals that stationary mitochondria within the axon interconnect with moving mitochondria through fusion and fission and that local inner membrane fusion between individual mitochondria mediates their global distribution.
Highlights
Mitochondria are essential organelles of eukaryotic cells, serving a wide variety of important functions that include energy production, metabolic regulation, and stress response[1,2]
Because dOpa[1] knockdown dramatically altered the balance between fusion and fission within the axon, we examined the morphology of axonal mitochondria
Individual mitochondria within the axon may appear as discrete compartments, they interconnect through fusion and fission as well as transport and anchoring to form a dynamic network
Summary
Mitochondria are essential organelles of eukaryotic cells, serving a wide variety of important functions that include energy production, metabolic regulation, and stress response[1,2]. To directly and quantitatively analyze relations between mitochondrial fusion/fission and spatial distribution, we developed high-resolution computational image analysis techniques to track movement and morphological changes of individual mitochondria and to characterize their fusion/fission and spatial behavior. Using our computational image analysis techniques, we analyzed in high-resolution relations between fusion/fission and spatial distribution of mitochondria within the axon of motor neurons in Drosophila third instar larvae under normal conditions and knockdown of dOpa[1], the Drosophila ortholog of human OPA122. Knockdown of dOpa[1] caused a dramatic imbalance between fusion and fission, which resulted in an overall increase in spatial density of stationary and moving mitochondria and in differential changes of their spatial distributions and morphology. Our data provides novel insights into the relations between local fusion/fission and global spatial distribution of the mitochondrial network
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