UNASSIGNED: Neurons rely on mitochondria as their preferred source of energy. Mutations in @entity193 and PARKIN cause @entity528 in early-onset @entity191 ( @entity191 ), thought to be due to @entity2383 . In Drosophila @entity193 and parkin mutants, @entity2383 lead to the compensatory upregulation of the mitochondrial one- @entity505 cycle metabolism genes by an unknown mechanism. Here we uncover that this branch is triggered by the @entity15205 ( @entity15205 ). We show that @entity15205 regulates the expression of one- @entity505 metabolism genes @entity68828 and @entity69181 as a protective response to @entity2383 . Suppressing @entity68828 or @entity69181 caused motor impairment and @entity2383 in flies. Epistatic analyses showed that suppressing the upregulation of @entity68828 or @entity69181 deteriorates the phenotype of @entity193 or parkin mutants. Conversely, the genetic enhancement of these one- @entity505 metabolism genes in @entity193 or parkin mutants was neuroprotective. We conclude that @entity2383 caused by mutations in the @entity193 /Parkin pathway engages @entity15205 -dependent activation of one- @entity505 metabolism as a protective response. Our findings show a central contribution of @entity15205 signalling to @entity191 that may represent a new therapeutic strategy. A video abstract for this article is available at https://youtu.be/cFJJm2YZKKM.Cell Death and Differentiation advance online publication, 17 February 2017; doi:10.1038/cdd.2016.158.

dATF4 regulation of mitochondrial folate-mediated one- XXXX metabolism is neuroprotective.

@entity68828 :: ('6472', 'Gene') :: ['Shmt2', 'SHMT2'] @entity15205 :: ('468', 'Gene') :: ['ATF4', 'activating transcription factor 4'] @entity191 :: ('MESH:D010300', 'Disease') :: ["Parkinson's disease", 'PD'] @entity193 :: ('65018', 'Gene') :: ['Pink1', 'pink1', 'PINK1'] @entity69181 :: ('10797', 'Gene') :: ['NMDMC', 'Nmdmc'] @entity505 :: ('MESH:D002244', 'Chemical') :: ['carbon'] @entity528 :: ('MESH:D009410', 'Disease') :: ['neuronal death'] @entity2383 :: ('MESH:D028361', 'Disease') :: ['mitochondrial dysfunction', 'mitochondrial defects', 'mitochondrial toxicity']
@entity505 :: (MESH:D002244,Chemical) :: ['carbon']
