Shaping the role of mitochondria in the pathogenesis of Huntington's disease
Open Access
- 23 March 2012
- journal article
- review article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 31 (8), 1853-1864
- https://doi.org/10.1038/emboj.2012.65
Abstract
Intense research on the pathogenesis of Huntington's disease (HD), a genetic neurodegenerative disease caused by a polyglutamine expansion in the Huntingtin (Htt) protein, revealed multiple potential mechanisms, among which mitochondrial alterations had emerged as key determinants of the natural history of the disease. Pharmacological and genetic animal models of mitochondrial dysfunction in the striatum, which is mostly affected in HD corroborated a key role for these organelles in the pathogenesis of the disease. Here, we will give an account of the recent evidence indicating that the mitochondria‐shaping machinery is altered in HD models and patients. Since its correction can counteract HD mitochondrial dysfunction and cellular damage, drugs impacting on mitochondrial shape are emerging as a new possibility of treatment for this devastating condition.Keywords
This publication has 158 references indexed in Scilit:
- Mitochondrial fission and cristae disruption increase the response of cell models of Huntington's disease to apoptotic stimuliEMBO Molecular Medicine, 2010
- Platelet Mitochondrial Complex I and I+III Activities Do Not Correlate with Cerebral Mitochondrial Oxidative MetabolismJournal of Cerebral Blood Flow & Metabolism, 2010
- Inhibition of transglutaminase 2 mitigates transcriptional dysregulation in models of Huntington diseaseEMBO Molecular Medicine, 2010
- S-Nitrosylation of Drp1 links excessive mitochondrial fission to neuronal injury in neurodegenerationMitochondrion, 2010
- Delivery of GABAARs to Synapses Is Mediated by HAP1-KIF5 and Disrupted by Mutant HuntingtinNeuron, 2010
- Complex II inhibition by 3-NP causes mitochondrial fragmentation and neuronal cell death via an NMDA- and ROS-dependent pathwayCell Death & Differentiation, 2009
- Mutant huntingtin and mitochondrial dysfunctionTrends in Neurosciences, 2008
- Chemical Inhibition of the Mitochondrial Division Dynamin Reveals Its Role in Bax/Bak-Dependent Mitochondrial Outer Membrane PermeabilizationDevelopmental Cell, 2008
- Cell DeathCell, 2004
- OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28Nature Genetics, 2000