Local mitochondrial replication in the periphery of neurons requires the eEF1A1 protein and thetranslation of nuclear-encoded proteins

Carlos Cardanho-Ramos, Rúben Alves Simões, Yi-Zhi Wang, Andreia Faria-Pereira, Ewa Bomba-Warczak, Katleen Craessaerts, Marco Spinazzi, Jeffrey N. Savas, Vanessa A. Morais*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

In neurons, it is commonly assumed that mitochondrial replication only occurs in the cell body, after which the mitochondria must travel to the neuron's periphery. However, while mitochondrial DNA replication has been observed to occur away from the cell body, the specific mechanisms involved remain elusive. Using EdU-labelling in mouse primary neurons, we developed a tool to determine the mitochondrial replication rate. Taking of advantage of microfluidic devices, we confirmed that mitochondrial replication also occurs locally in the periphery of neurons. To achieve this, mitochondria require de novo nuclear-encoded, but not mitochondrial-encoded protein translation. Following a proteomic screen comparing synaptic with non-synaptic mitochondria, we identified two elongation factors – eEF1A1 and TUFM – that were upregulated in synaptic mitochondria. We found that mitochondrial replication is impaired upon the downregulation of eEF1A1, and this is particularly relevant in the periphery of neurons.

Original languageEnglish (US)
Article number109136
JournaliScience
Volume27
Issue number4
DOIs
StatePublished - Apr 19 2024

Keywords

  • Biochemistry
  • Biological sciences
  • Cellular neuroscience
  • Molecular neuroscience
  • Natural sciences
  • Neuroscience

ASJC Scopus subject areas

  • General

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