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Nat Commun. 2018 Nov 27;9(1):5008. doi: 10.1038/s41467-018-07416-2.

MFF-dependent mitochondrial fission regulates presynaptic release and axon branching by limiting axonal mitochondria size.

Lewis TL Jr1,2,3, Kwon SK1,2,4, Lee A1,2, Shaw R5, Polleux F6,7,8.

Author information

1
Department of Neuroscience, Columbia University, New York, NY, 10032, USA.
2
Mortimer B. Zuckerman Mind Brain Behavior Institute, New York, NY, 10032, USA.
3
Aging & Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.
4
Center for Functional Connectomics, Brain Science Institute, Korea Institute of Science and Technology, Seoul, 02792, South Korea.
5
Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.
6
Department of Neuroscience, Columbia University, New York, NY, 10032, USA. fp2304@cumc.columbia.edu.
7
Mortimer B. Zuckerman Mind Brain Behavior Institute, New York, NY, 10032, USA. fp2304@cumc.columbia.edu.
8
Kavli Institute for Brain Science at Columbia University, New York, NY, 10032, USA. fp2304@cumc.columbia.edu.

Abstract

Neurons display extreme degrees of polarization, including compartment-specific organelle morphology. In cortical, long-range projecting, pyramidal neurons (PNs), dendritic mitochondria are long and tubular whereas axonal mitochondria display uniformly short length. Here we explored the functional significance of maintaining small mitochondria for axonal development in vitro and in vivo. We report that the Drp1 'receptor' Mitochondrial fission factor (MFF) is required for determining the size of mitochondria entering the axon and then for maintenance of their size along the distal portions of the axon without affecting their trafficking properties, presynaptic capture, membrane potential or ability to generate ATP. Strikingly, this increase in presynaptic mitochondrial size upon MFF downregulation augments their capacity for Ca2+ ([Ca2+]m) uptake during neurotransmission, leading to reduced presynaptic [Ca2+]c accumulation, decreased presynaptic release and terminal axon branching. Our results uncover a novel mechanism controlling neurotransmitter release and axon branching through fission-dependent regulation of presynaptic mitochondrial size.

PMID:
30479337
PMCID:
PMC6258764
DOI:
10.1038/s41467-018-07416-2
[Indexed for MEDLINE]
Free PMC Article

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