Dendritic mitochondria reach stable positions during circuit development.

Michelle C Faits,Chunmeng Zhang,Florentina Soto,Daniel Kerschensteiner

doi:10.7554/elife.11583

Abstract

Mitochondria move throughout neuronal dendrites and localize to sites of energy demand. The prevailing view of dendritic mitochondria as highly motile organelles whose distribution is continually adjusted by neuronal activity via Ca(2+)-dependent arrests is based on observations in cultured neurons exposed to artificial stimuli. Here, we analyze the movements of mitochondria in ganglion cell dendrites in the intact retina. We find that whereas during development 30% of mitochondria are motile at any time, as dendrites mature, mitochondria all but stop moving and localize stably to synapses and branch points. Neither spontaneous nor sensory-evoked activity and Ca(2+) transients alter motility of dendritic mitochondria; and pathological hyperactivity in a mouse model of retinal degeneration elevates rather than reduces motility. Thus, our findings indicate that dendritic mitochondria reach stable positions during a critical developmental period of high motility, and challenge current views about the role of activity in regulating mitochondrial transport in dendrites.

Highlights

Mitochondria provide energy in the form of ATP and phosphocreatine, and participate in Ca2+ signaling
We find that mitochondrial density in retinal ganglion cell (RGC) dendrites reaches near-mature levels before most synapses are formed
Using simultaneous two-photon imaging of mitochondrial movements and intracellular Ca2+, we find that elevation of external K+ reduces motility of dendritic mitochondria in the retina as it does in cultured neurons, neither spontaneous waves of activity during development, nor sensory-evoked activity at maturity alter the motility of dendritic mitochondria in RGCs

Summary

Introduction

Mitochondria provide energy in the form of ATP and phosphocreatine, and participate in Ca2+ signaling. Mitochondrial biosynthesis occurs in the soma, but sites of energy use and Ca2+ influx are dispersed across axonal and dendritic arbors (Davis and Clayton, 1996). To meet these distributed demands, neuronal mitochondria are transported throughout axons and dendrites along microtubule tracks (Ehlers, 2013; Lin and Sheng, 2015). Increased ER complexity and Golgi outposts at dendritic branch points support protein and lipid biosynthesis, and secretory trafficking (CuiWang et al, 2012; Ehlers, 2013; Horton et al, 2005; Ye et al, 2007).

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