RRC ID 49579
著者 Tsuyama T, Tsubouchi A, Usui T, Imamura H, Uemura T.
タイトル Mitochondrial dysfunction induces dendritic loss via eIF2α phosphorylation.
ジャーナル J Cell Biol
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.
巻・号 216(3)
ページ 815-834
公開日 2017-3-6
DOI 10.1083/jcb.201604065
PII jcb.201604065
PMID 28209644
PMC PMC5346966
MeSH Adenosine Triphosphate / metabolism Animals Dendrites / metabolism Dendrites / pathology Drosophila melanogaster / metabolism Drosophila melanogaster / pathogenicity Eukaryotic Initiation Factor-2 / metabolism* Mitochondria / metabolism* Mitochondria / pathology* Mitochondrial Diseases / metabolism* Mitochondrial Diseases / pathology* Neurons / metabolism Neurons / pathology Phosphorylation / physiology*
IF 8.811
引用数 12
リソース情報
ショウジョウバエ 調査中