UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Pathogenic VCP Mutations Induce Mitochondrial Uncoupling and Reduced ATP Levels
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Bartolome F, Wu HC, Burchell VS, Preza E, Wray S, Mahoney CJ, Fox NC, Calvo A, Canosa A, Moglia C, Mandrioli J, ChiĆ² A, Orrell RW, Houlden H, Hardy J, Abramov AY, Plun-Favreau H
  • Publication date:
    10/04/2013
  • Pagination:
    57, 64
  • Journal:
    Neuron
  • Volume:
    78
  • Issue:
    1
  • Status:
    Published
  • Print ISSN:
    0896-6273
Abstract
Valosin-containing protein (VCP) is a highly expressed member of the type II AAA+ ATPase family. VCP mutations are the cause of inclusion body myopathy, Paget@s disease of the bone, and frontotemporal dementia (IBMPFD) and they account for 1%-2% of familial amyotrophic lateral sclerosis (ALS). Using fibroblasts from patients carrying three independent pathogenic mutations in the VCP gene, we show that VCP deficiency causes profound mitochondrial uncoupling leading to decreased mitochondrial membrane potential and increased mitochondrial oxygen consumption. This mitochondrial uncoupling results in a significant reduction of cellular ATP production. Decreased ATP levels in VCP-deficient cells lower their energy capacity, making them more vulnerable to high energy-demanding processes such as ischemia. Our findings propose a mechanism by which pathogenic VCP mutations lead to cell death
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers Show More
Author
Clinical and Movement Neurosciences
Author
Neurodegenerative Diseases
Author
Neurodegenerative Diseases
Author
Department of Neuromuscular Diseases
Author
Clinical and Movement Neurosciences
Author
Neurodegenerative Diseases
Author
Neurodegenerative Diseases
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by