| Autor: |
Virga DM; Department of Neuroscience, Columbia Medical School, New York, NY- USA.; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY- USA., Hamilton S; Department of Neuroscience, Columbia Medical School, New York, NY- USA.; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY- USA., Osei B; Aging & Metabolism Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA., Morgan A; Aging & Metabolism Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.; Neuroscience, Oklahoma University Health Science Campus, Oklahoma City, OK, USA., Zamponi E; Department of Neuroscience, Columbia Medical School, New York, NY- USA.; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY- USA., Park NJ; Department of Neuroscience, Columbia Medical School, New York, NY- USA.; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY- USA., Hewitt VL; Department of Neuroscience, Columbia Medical School, New York, NY- USA.; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY- USA., Zhang D; Department of Neuroscience, Columbia Medical School, New York, NY- USA.; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY- USA., Gonzalez KC; Department of Neuroscience, Columbia Medical School, New York, NY- USA.; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY- USA., Bloss E; The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA., Polleux F; Department of Neuroscience, Columbia Medical School, New York, NY- USA.; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY- USA., Lewis TL Jr; Aging & Metabolism Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.; Neuroscience, Oklahoma University Health Science Campus, Oklahoma City, OK, USA. |
| Abstrakt: |
Neuronal mitochondria play important roles beyond ATP generation, including Ca 2+ uptake, and therefore have instructive roles in synaptic function and neuronal response properties. Mitochondrial morphology differs significantly in the axon and dendrites of a given neuronal subtype, but in CA1 pyramidal neurons (PNs) of the hippocampus, mitochondria within the dendritic arbor also display a remarkable degree of subcellular, layer-specific compartmentalization. In the dendrites of these neurons, mitochondria morphology ranges from highly fused and elongated in the apical tuft, to more fragmented in the apical oblique and basal dendritic compartments, and thus occupy a smaller fraction of dendritic volume than in the apical tuft. However, the molecular mechanisms underlying this striking degree of subcellular compartmentalization of mitochondria morphology are unknown, precluding the assessment of its impact on neuronal function. Here, we demonstrate that this compartment-specific morphology of dendritic mitochondria requires activity-dependent, Camkk2-dependent activation of AMPK and its ability to phosphorylate two direct effectors: the pro-fission Drp1 receptor Mff and the recently identified anti-fusion, Opa1-inhibiting protein, Mtfr1l. Our study uncovers a new activity-dependent molecular mechanism underlying the extreme subcellular compartmentalization of mitochondrial morphology in dendrites of neurons in vivo through spatially precise regulation of mitochondria fission/fusion balance. |
