title: Inner membrane fusion mediates spatial distribution of axonal mitochondria.
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.
authors.affiliation: Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213.|Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, PA 15213.
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213.
authors.forename: Hao-Chih
authors.initials: HC
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213.
authors.forename: Kuan-Chieh
authors.initials: KC
authors.lastname: Chen
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213.
authors.forename: Joseph
authors.initials: J
authors.lastname: Suhan
authors.affiliation: Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213.
authors.forename: Minhua
authors.initials: M
authors.lastname: Qiu
authors.affiliation: Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213.
authors.forename: Qinle
authors.initials: Q
authors.lastname: Ba
authors.affiliation: Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213.|Department of Computational Biology, Carnegie Mellon University, Pittsburgh, PA 15213.
authors.forename: Ge
authors.initials: G
authors.lastname: Yang
mesh_terms: D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000235:genetics / Q000378:metabolism; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D063154:Mitochondrial Dynamics / Q000235:genetics*; D051336:Mitochondrial Membranes / Q000378:metabolism* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C527116:OPA1 protein, Drosophila; D034741:RNA, Small Interfering; C470348:milt protein, Drosophila; C515209:Khc protein, Drosophila; D016547:Kinesins