Academic Journal
Pathogenic VCP mutations induce mitochondrial uncoupling and reduced ATP levels
| العنوان: | Pathogenic VCP mutations induce mitochondrial uncoupling and reduced ATP levels |
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| المؤلفون: | Bartolome F, Wu HC, Burchell VS, Preza E, Wray S, Mahoney CJ, Fox NC, Calvo A, Canosa A, Moglia C, Mandrioli J, Chiò A, Orrell RW, Houlden H, Hardy J, Abramov AY, Plun-Favreau H. |
| المساهمون: | Bartolome, F, Wu, Hc, Burchell, V, Preza, E, Wray, S, Mahoney, Cj, Fox, Nc, Calvo, A, Canosa, A, Moglia, C, Mandrioli, J, Chiò, A, Orrell, Rw, Houlden, H, Hardy, J, Abramov, Ay, Plun-Favreau, H. |
| سنة النشر: | 2013 |
| المجموعة: | Archivio della ricerca dell'Università di Modena e Reggio Emilia (Unimore: IRIS) |
| الوصف: | 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. Copyright © 2013 Elsevier Inc. All rights reserved. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/23498975; info:eu-repo/semantics/altIdentifier/wos/WOS:000317556000007; volume:78; issue:1; firstpage:57; lastpage:64; numberofpages:8; journal:NEURON; http://hdl.handle.net/11380/1237953; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84876079328 |
| DOI: | 10.1016/j.neuron.2013.02.028 |
| الاتاحة: | http://hdl.handle.net/11380/1237953 https://doi.org/10.1016/j.neuron.2013.02.028 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.ED2F9E0A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.neuron.2013.02.028 |
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