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

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...

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Published iniScience Vol. 27; no. 4; p. 109136
Main Authors Cardanho-Ramos, Carlos, Simões, Rúben Alves, Wang, Yi-Zhi, Faria-Pereira, Andreia, Bomba-Warczak, Ewa, Craessaerts, Katleen, Spinazzi, Marco, Savas, Jeffrey N., Morais, Vanessa A.
Format Journal Article
LanguageEnglish
Published Elsevier Inc 19.04.2024
Subjects
Biochemistry
Biological sciences
Cellular neuroscience
Molecular neuroscience
Natural sciences
Neuroscience
Molecular neuroscience
Neuroscience
Biochemistry
Biological sciences
Natural sciences
Cellular neuroscience
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Summary: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. [Display omitted] •Mitochondrial replication occurs in distal regions of neurons•Mitochondrial-encoded translation is not required for mtDNA replication in neurons•In neurons, mitochondrial replication requires nuclear-encoded protein translation•EEF1A1 is upregulated at the synapse and is required for mitochondrial replication Biochemistry; Biological sciences; Cellular neuroscience; Molecular neuroscience; Natural sciences; Neuroscience
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2024.109136