TY - JOUR T1 - Loss of Mitochondrial Fission Depletes Axonal Mitochondria in Midbrain Dopamine Neurons JF - The Journal of Neuroscience JO - J. Neurosci. SP - 14304 LP - 14317 DO - 10.1523/JNEUROSCI.0930-14.2014 VL - 34 IS - 43 AU - Amandine Berthet AU - Elyssa B. Margolis AU - Jue Zhang AU - Ivy Hsieh AU - Jiasheng Zhang AU - Thomas S. Hnasko AU - Jawad Ahmad AU - Robert H. Edwards AU - Hiromi Sesaki AU - Eric J. Huang AU - Ken Nakamura Y1 - 2014/10/22 UR - http://www.jneurosci.org/content/34/43/14304.abstract N2 - 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. ER -