title: 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 inDrosophila melanogasterclass 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.
authors.affiliation: Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Taiichi
authors.initials: T
authors.lastname: Tsuyama
authors.affiliation: Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Tsubouchi
authors.affiliation: Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Tadao
authors.identifier: 0000-0002-0507-1495
authors.initials: T
authors.lastname: Usui
authors.affiliation: Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Imamura
authors.affiliation: Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan tauemura@lif.kyoto-u.ac.jp.
authors.forename: Tadashi
authors.identifier: 0000-0001-7204-3606
authors.initials: T
authors.lastname: Uemura
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003712:Dendrites / Q000378:metabolism / Q000473:pathology; D004331:Drosophila melanogaster / Q000378:metabolism / Q000472:pathogenicity; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology*; D028361:Mitochondrial Diseases / Q000378:metabolism* / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000502:physiology*
chemical_list: D015852:Eukaryotic Initiation Factor-2; D000255:Adenosine Triphosphate