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Loss of mitochondrial fission depletes axonal mitochondria in midbrain dopamine neurons.


ABSTRACT: Disruptions in mitochondrial dynamics may contribute to the selective degeneration of dopamine (DA) neurons in Parkinson's disease (PD). However, little is known about the normal functions of mitochondrial dynamics in these neurons, especially in axons where degeneration begins, and this makes it difficult to understand the disease process. To study one aspect of mitochondrial dynamics-mitochondrial fission-in mouse DA neurons, we deleted the central fission protein dynamin-related protein 1 (Drp1). Drp1 loss rapidly eliminates the DA terminals in the caudate-putamen and causes cell bodies in the midbrain to degenerate and lose ?-synuclein. Without Drp1, mitochondrial mass dramatically decreases, especially in axons, where the mitochondrial movement becomes uncoordinated. However, in the ventral tegmental area (VTA), a subset of midbrain DA neurons characterized by small hyperpolarization-activated cation currents (Ih) is spared, despite near complete loss of their axonal mitochondria. Drp1 is thus critical for targeting mitochondria to the nerve terminal, and a disruption in mitochondrial fission can contribute to the preferential death of nigrostriatal DA neurons.

SUBMITTER: Berthet A 

PROVIDER: S-EPMC4205554 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Loss of mitochondrial fission depletes axonal mitochondria in midbrain dopamine neurons.

Berthet Amandine A   Margolis Elyssa B EB   Zhang Jue J   Hsieh Ivy I   Zhang Jiasheng J   Hnasko Thomas S TS   Ahmad Jawad J   Edwards Robert H RH   Sesaki Hiromi H   Huang Eric J EJ   Nakamura Ken K  

The Journal of neuroscience : the official journal of the Society for Neuroscience 20141001 43


Disruptions in mitochondrial dynamics may contribute to the selective degeneration of dopamine (DA) neurons in Parkinson's disease (PD). However, little is known about the normal functions of mitochondrial dynamics in these neurons, especially in axons where degeneration begins, and this makes it difficult to understand the disease process. To study one aspect of mitochondrial dynamics-mitochondrial fission-in mouse DA neurons, we deleted the central fission protein dynamin-related protein 1 (Dr  ...[more]

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