Spatially Stable Mitochondrial Compartments Fuel Local Translation during Plasticity

Cell. 2019 Jan 10;176(1-2):73-84.e15. doi: 10.1016/j.cell.2018.12.013. Epub 2019 Jan 3.

Abstract

Local translation meets protein turnover and plasticity demands at synapses, however, the location of its energy supply is unknown. We found that local translation in neurons is powered by mitochondria and not by glycolysis. Super-resolution microscopy revealed that dendritic mitochondria exist as stable compartments of single or multiple filaments. To test if these mitochondrial compartments can serve as local energy supply for synaptic translation, we stimulated individual synapses to induce morphological plasticity and visualized newly synthesized proteins. Depletion of local mitochondrial compartments abolished both the plasticity and the stimulus-induced synaptic translation. These mitochondrial compartments serve as spatially confined energy reserves, as local depletion of a mitochondrial compartment did not affect synaptic translation at remote spines. The length and stability of dendritic mitochondrial compartments and the spatial functional domain were altered by cytoskeletal disruption. These results indicate that cytoskeletally tethered local energy compartments exist in dendrites to fuel local translation during synaptic plasticity.

Keywords: ATP; compartments; cytoskeleton; energy; local translation; mitochondria; nascent protein; protein synthesis; synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytoskeleton / metabolism
  • Dendrites / metabolism
  • Dendritic Spines / metabolism
  • Female
  • Male
  • Mitochondria / metabolism*
  • Mitochondria / physiology
  • Neuronal Plasticity / physiology
  • Neurons / metabolism*
  • Protein Biosynthesis / physiology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Synapses / metabolism

Substances

  • RNA, Messenger