PXD041846

PXD041846 is an original dataset announced via ProteomeXchange.

Title	Mutant Huntingtin impairs neurodevelopment in human brain organoids through CHCHD2-mediated neurometabolic failure
Description	Expansion of the poly-glutamine (Q) tract in the protein Huntingtin (HTT) causes the neurodegenerative disorder Huntington’s disease (HD). Emerging evidence suggests that mutant HTT (mHTT) disrupts brain development. To gain mechanistic insights into the neurodevelopmental impact of human mHTT, we engineered induced pluripotent stem cells to introduce a 70Q expansion or remove the poly-Q tract. mHTT introduction caused aberrant development of cerebral organoids with loss of neural progenitor organization. The early neurodevelopmental signature of mHTT highlighted the dysregulation of coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2), which is involved in mitochondrial integrated stress response. CHCHD2 repression was associated with abnormal mitochondrial morpho-dynamics and elevated resting energy expenditure. Elimination of the poly-Q tract reverted CHCHD2 expression and mitochondrial defects. Hence, mHTT-mediated disruption of human neurodevelopment is paralleled by aberrant neurometabolic programming mediated by dysregulation of CHCHD2, which could then represent a target of early intervention for HD.
HostingRepository	PRIDE
AnnounceDate	2024-06-21
AnnouncementXML	Submission_2024-06-21_01:46:08.672.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Meierhofer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	carbamoylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-27 01:46:36	ID requested
⏵ 1	2024-06-21 01:46:09	announced

Dataset with its publication pending

submitter keyword: Huntington’s disease, Huntingtin (HTT), brain development

Alessandro Prigione
contact affiliation	Department of General Pediatrics, Neonatology and Pediatric Cardiology, Heinrich Heine University, Medical Faculty, Düsseldorf, Germany
contact email	alessandro.prigione@hhu.de
lab head
David Meierhofer
contact affiliation	Mass Spectrometry Facility MPIMG
contact email	meierhof@molgen.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041846
     1. Label: PRIDE project
     2. Name: Mutant Huntingtin impairs neurodevelopment in human brain organoids through CHCHD2-mediated neurometabolic failure