RT Journal Article
SR Electronic
T1 Loss of Mitochondrial Fission Depletes Axonal Mitochondria in Midbrain Dopamine Neurons
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 14304
OP 14317
DO 10.1523/JNEUROSCI.0930-14.2014
VO 34
IS 43
A1 Amandine Berthet
A1 Elyssa B. Margolis
A1 Jue Zhang
A1 Ivy Hsieh
A1 Jiasheng Zhang
A1 Thomas S. Hnasko
A1 Jawad Ahmad
A1 Robert H. Edwards
A1 Hiromi Sesaki
A1 Eric J. Huang
A1 Ken Nakamura
YR 2014
UL http://www.jneurosci.org/content/34/43/14304.abstract
AB 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 α-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.