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Mitochondrial dysfunction induces dendritic loss via eIF2α phosphorylation.

ABSTRACT: Mitochondria are key contributors to the etiology of diseases associated with neuromuscular defects or neurodegeneration. How changes in cellular metabolism specifically impact neuronal intracellular processes and cause neuropathological events is still unclear. We here dissect the molecular mechanism by which mitochondrial dysfunction induced by Prel aberrant function mediates selective dendritic loss in Drosophila melanogaster class IV dendritic arborization neurons. Using in vivo ATP imaging, we found that neuronal cellular ATP levels during development are not correlated with the progression of dendritic loss. We searched for mitochondrial stress signaling pathways that induce dendritic loss and found that mitochondrial dysfunction is associated with increased eIF2α phosphorylation, which is sufficient to induce dendritic pathology in class IV arborization neurons. We also observed that eIF2α phosphorylation mediates dendritic loss when mitochondrial dysfunction results from other genetic perturbations. Furthermore, mitochondrial dysfunction induces translation repression in class IV neurons in an eIF2α phosphorylation-dependent manner, suggesting that differential translation attenuation among neuron subtypes is a determinant of preferential vulnerability.

SUBMITTER: Tsuyama T

PROVIDER: S-EPMC5346966 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Mitochondrial dysfunction induces dendritic loss via eIF2α phosphorylation.

Tsuyama Taiichi T Tsubouchi Asako A Usui Tadao T Imamura Hiromi H Uemura Tadashi T

The Journal of cell biology 20170216 3

Mitochondria are key contributors to the etiology of diseases associated with neuromuscular defects or neurodegeneration. How changes in cellular metabolism specifically impact neuronal intracellular processes and cause neuropathological events is still unclear. We here dissect the molecular mechanism by which mitochondrial dysfunction induced by Prel aberrant function mediates selective dendritic loss in <i>Drosophila melanogaster</i> class IV dendritic arborization neurons. Using in vivo ATP i ...[more]

PMID: 28209644

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Dataset Information

Mitochondrial dysfunction induces dendritic loss via eIF2α phosphorylation.

Publications

Mitochondrial dysfunction induces dendritic loss via eIF2α phosphorylation.

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