TY - JOUR
T1 - Deletion of DJ-1 in rats affects protein abundance and mitochondrial function at the synapse
AU - Almikhlafi, Mohannad A.
AU - Stauch, Kelly L.
AU - Villeneuve, Lance M.
AU - Purnell, Phillip R.
AU - Lamberty, Benjamin G.
AU - Fox, Howard S.
N1 - Funding Information:
This study was supported by a Michael J. Fox Foundation (MJFF) Grant #9524, in addition to the NIH, National Institute of Mental Health, P30MH062261. The content is solely the responsibility of the authors and does not necessarily represent the official views of the MJFF or the NIH. We are grateful for technical support received from the UNMC Mass Spectrometry and Proteomics Core Facility. The graduate studies of Mohannad Almikhlafi were graciously supported by the Saudi Arabian Cultural Mission and Taibah University.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - DJ-1 is a multifunctional protein affecting different biological and cellular processes. In addition, DJ-1 has roles in regulating mitochondrial function. Loss-of-function mutations in DJ-1 were found to cause an autosomal recessive form of Parkinson’s disease. One of the main pathological features of PD is loss of dopamine neurons in the nigrostriatal pathway. DJ-1 knockout (KO) rats exhibit progressive nigral neurodegeneration with about 50% dopaminergic cell loss at 8 months of age. In order to assess the effects of DJ-1 deficiency on neuronal mitochondria prior to neuron loss, we performed proteomic analysis of synaptic mitochondria isolated from the striatum, the location of nigrostriatal pathway nerve terminals, of 3-month-old DJ-1 KO rats. In total, 371 mitochondrial proteins were quantified, and of these 76 were differentially expressed in DJ-1 KO rats. Proteins perturbed by the loss of DJ-1 were involved in several mitochondrial functional pathways, including the tricarboxylic acid cycle and electron transport chain. Thus, synaptic mitochondrial respiration was measured and showed a significant change due to DJ-1 deficiency. The dataset generated here highlights the role of synaptic mitochondria in PD associated with DJ-1. This study improves our understanding of DJ-1 effects in a complex tissue environment and the synaptic mitochondrial changes that accompany its loss.
AB - DJ-1 is a multifunctional protein affecting different biological and cellular processes. In addition, DJ-1 has roles in regulating mitochondrial function. Loss-of-function mutations in DJ-1 were found to cause an autosomal recessive form of Parkinson’s disease. One of the main pathological features of PD is loss of dopamine neurons in the nigrostriatal pathway. DJ-1 knockout (KO) rats exhibit progressive nigral neurodegeneration with about 50% dopaminergic cell loss at 8 months of age. In order to assess the effects of DJ-1 deficiency on neuronal mitochondria prior to neuron loss, we performed proteomic analysis of synaptic mitochondria isolated from the striatum, the location of nigrostriatal pathway nerve terminals, of 3-month-old DJ-1 KO rats. In total, 371 mitochondrial proteins were quantified, and of these 76 were differentially expressed in DJ-1 KO rats. Proteins perturbed by the loss of DJ-1 were involved in several mitochondrial functional pathways, including the tricarboxylic acid cycle and electron transport chain. Thus, synaptic mitochondrial respiration was measured and showed a significant change due to DJ-1 deficiency. The dataset generated here highlights the role of synaptic mitochondria in PD associated with DJ-1. This study improves our understanding of DJ-1 effects in a complex tissue environment and the synaptic mitochondrial changes that accompany its loss.
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U2 - 10.1038/s41598-020-70486-0
DO - 10.1038/s41598-020-70486-0
M3 - Article
C2 - 32792613
AN - SCOPUS:85089392333
VL - 10
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 13719
ER -