We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Loss of Mitochondrial Fission Depletes Axonal Mitochondria in Midbrain Dopamine Neurons.
- Authors
Berthet, Amandine; Margolis, Elyssa B.; Jue Zhang; Hsieh, Ivy; Jiasheng Zhang; Hnasko, Thomas S.; Ahmad, Jawad; Edwards, Robert H.; Hiromi Sesaki; Huang, Eric J.; Ken Nakamura
- 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 (Drp 1 ). Drp 1 loss rapidly eliminates the DA terminals in the caudate-putamen and causes cell bodies in the midbrain to degenerate and lose a-synuclein. Without Drpl, 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. Drpl 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.
- Subjects
MESENCEPHALON; DOPAMINERGIC neurons; MITOCHONDRIAL physiology; MITOCHONDRIAL dynamics; NEURODEGENERATION; DYNAMIN (Genetics); AXONS
- Publication
Journal of Neuroscience, 2014, Vol 34, Issue 43, p14304
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0930-14.2014