The 7q11.23 Protein DNAJC30 Interacts with ATP Synthase and Links Mitochondria to Brain Development. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • November 1, 2018

Research

keywords

  • ATP Synthetase Complexes
  • Brain
  • HSP40 Heat-Shock Proteins
  • Mitochondria
  • Williams Syndrome

Identity

PubMed Central ID

  • PMC6459420

Scopus Document Identifier

  • 85056053521

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2018.09.014

PubMed ID

  • 30318146

Additional Document Info

volume

  • 175

issue

  • 4