Document Type
Article
Publication Date
3-8-2024
Original Citation
Virga D,
Hamilton S,
Osei B,
Morgan A,
Kneis P,
Zamponi E,
Park N,
Hewitt V,
Zhang D,
Gonzalez K,
Russell F,
Grahame Hardie D,
Prudent J,
Bloss E,
Losonczy A,
Polleux F,
Lewis T.
Activity-dependent compartmentalization of dendritic mitochondria morphology through local regulation of fusion-fission balance in neurons in vivo. Nat Commun. 2024;15(1):2142.
Keywords
JMG, Neurons, Pyramidal Cells, Hippocampus, Axons, Mitochondria, Dendrites
JAX Source
Nat Commun. 2024;15(1):2142.
ISSN
2041-1723
PMID
38459070
DOI
https://doi.org/10.1038/s41467-024-46463-w
Grant
HHMI/Janelia (EB)
Abstract
Neuronal mitochondria play important roles beyond ATP generation, includ- ing Ca2+ uptake, and therefore have instructive roles in synaptic function and neuronal response properties. Mitochondrial morphology differs significantly between the axon and dendrites of a given neuronal subtype, but in CA1 pyr- amidal neurons (PNs) of the hippocampus, mitochondria within the dendritic arbor also display a remarkable degree of subcellular, layer-specific compart- mentalization. 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 com- partmentalization 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 activ- ity-dependent, Ca2+ and 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 signaling pathway underlying the subcellular compartmentaliza- tion of mitochondrial morphology in dendrites of neurons in vivo through spatially precise and activity-dependent regulation of mitochondria fission/ fusion balance.
Comments
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