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The 7q11.23 Protein DNAJC30 Interacts with ATP Synthase and Links Mitochondria to Brain Development
- Publication Year :
- 2018
-
Abstract
- Summary Despite the known causality of copy-number variations (CNVs) to human neurodevelopmental disorders, the mechanisms behind each gene’s contribution to the constellation of neural phenotypes remain elusive. Here, we investigated the 7q11.23 CNV, whose hemideletion causes Williams syndrome (WS), and uncovered that mitochondrial dysfunction participates in WS pathogenesis. Dysfunction is facilitated in part by the 7q11.23 protein DNAJC30, which interacts with mitochondrial ATP-synthase machinery. Removal of Dnajc30 in mice resulted in hypofunctional mitochondria, diminished morphological features of neocortical pyramidal neurons, and altered behaviors reminiscent of WS. The mitochondrial features are consistent with our observations of decreased integrity of oxidative phosphorylation supercomplexes and ATP-synthase dimers in WS. Thus, we identify DNAJC30 as an auxiliary component of ATP-synthase machinery and reveal mitochondrial maladies as underlying certain defects in brain development and function associated with WS.
- Subjects :
- 0301 basic medicine
Male
Williams Syndrome
Oxidative phosphorylation
Mitochondrion
General Biochemistry, Genetics and Molecular Biology
Oxidative Phosphorylation
Article
03 medical and health sciences
Mice
medicine
Animals
Humans
Gene
Cells, Cultured
ATP synthase
biology
HEK 293 cells
Brain
HSP40 Heat-Shock Proteins
medicine.disease
Phenotype
Macaca mulatta
Cell biology
Mitochondria
ATP Synthetase Complexes
Mice, Inbred C57BL
030104 developmental biology
HEK293 Cells
biology.protein
Female
Williams syndrome
Function (biology)
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....0eb9724a1c7e542fbc861619a39f2c46