Retrograde Mitochondrial Transport Is Essential for Organelle Distribution and Health in Zebrafish Neurons

作者：Amrita Mandal, Hiu-Tung Wong, Katherine Pinter, Natalie Mosqueda, Alisha Beirl, Richa Madan Lomash, Sehoon Won, Katie S. Kindt, Catherine M. Drerup · 发表于：Journal of Neuroscience · 年份：2020 · DOI：10.1523/jneurosci.1316-20.2020 · 被引用次数：74 · 研究领域：Mitochondrial Function and Pathology、Autophagy in Disease and Therapy、Neuroscience and Neuropharmacology Research

In neurons, mitochondria are transported by molecular motors throughout the cell to form and maintain functional neural connections. These organelles have many critical functions in neurons and are of high interest as their dysfunction is associated with disease. While the mechanics and impact of anterograde mitochondrial movement toward axon terminals are beginning to be understood, the frequency and function of retrograde (cell body directed) mitochondrial transport in neurons are still largely unexplored. While existing evidence indicates that some mitochondria are retrogradely transported for degradation in the cell body, the precise impact of disrupting retrograde transport on the organelles and the axon was unknown. Using long-term, in vivo imaging, we examined mitochondrial motility in zebrafish sensory and motor axons. We show that retrograde transport of mitochondria from axon terminals allows replacement of the axon terminal population within a day. By tracking these organelles, we show that not all mitochondria that leave the axon terminal are degraded; rather, they persist over several days. Disrupting retrograde mitochondrial flux in neurons leads to accumulation of aged organelles in axon terminals and loss of cell body mitochondria. Assays of neural circuit activity demonstrated that disrupting mitochondrial transport and function has no effect on sensory axon terminal activity but does negatively impact motor neuron axons. Taken together, our work supports a p...