Activity-dependent compartmentalization of dendritic mitochondria morphology through local regulation of fusion-fission balance in neurons in vivo

Daniel M. Virga, Stevie Hamilton, Bertha Osei, Abigail Morgan, Parker Kneis, Emiliano Zamponi, Natalie J. Park, Victoria L. Hewitt, David Zhang, Kevin C. Gonzalez, Fiona M. Russell, D. Grahame Hardie, Julien Prudent, Erik Bloss, Attila Losonczy, Franck Polleux () and Tommy L. Lewis ()
Additional contact information
Daniel M. Virga: Columbia University
Stevie Hamilton: Columbia University
Bertha Osei: Oklahoma Medical Research Foundation
Abigail Morgan: Oklahoma Medical Research Foundation
Parker Kneis: Oklahoma Medical Research Foundation
Emiliano Zamponi: Columbia University
Natalie J. Park: Columbia University
Victoria L. Hewitt: Columbia University
David Zhang: Columbia University
Kevin C. Gonzalez: Columbia University
Fiona M. Russell: University of Dundee
D. Grahame Hardie: University of Dundee
Julien Prudent: University of Cambridge
Erik Bloss: The Jackson Laboratory
Attila Losonczy: Columbia University
Franck Polleux: Columbia University
Tommy L. Lewis: Oklahoma Medical Research Foundation

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: Abstract Neuronal mitochondria play important roles beyond ATP generation, including 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 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, 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 compartmentalization of mitochondrial morphology in dendrites of neurons in vivo through spatially precise and activity-dependent regulation of mitochondria fission/fusion balance.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-46463-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46463-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-46463-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().