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Raft-like microdomains play a key role in mitochondrial impairment in lymphoid cells from patients with Huntington's disease.
- Source :
-
Journal of lipid research [J Lipid Res] 2012 Oct; Vol. 53 (10), pp. 2057-2068. Date of Electronic Publication: 2012 Jul 06. - Publication Year :
- 2012
-
Abstract
- Huntington's disease (HD) is a genetic neurodegenerative disease characterized by an exceedingly high number of contiguous glutamine residues in the translated protein, huntingtin (Htt). The primary site of cell toxicity is the nucleus, but mitochondria have been identified as key components of cell damage. The present work has been carried out in immortalized lymphocytes from patients with HD. These cells, in comparison with lymphoid cells from healthy subjects, displayed: i) a redistribution of mitochondria, forming large aggregates; ii) a constitutive hyperpolarization of mitochondrial membrane; and iii) a constitutive alteration of mitochondrial fission machinery, with high apoptotic susceptibility. Moreover, mitochondrial fission molecules, e.g., protein dynamin-related protein 1, as well as Htt, associated with mitochondrial raft-like microdomains, glycosphingolipid-enriched structures detectable in mitochondria. These findings, together with the observation that a ceramide synthase inhibitor and a raft disruptor are capable of impairing the peculiar mitochondrial remodeling in HD cells, suggest that mitochondrial alterations occurring in these cells could be due to raft-mediated defects of mitochondrial fission/fusion machinery.
- Subjects :
- Apoptosis
Dynamins
Fluorescent Antibody Technique
GTP Phosphohydrolases genetics
GTP Phosphohydrolases metabolism
Humans
Huntingtin Protein
Huntington Disease genetics
Lymphocytes ultrastructure
Microscopy, Electron, Transmission
Microscopy, Immunoelectron
Microtubule-Associated Proteins genetics
Microtubule-Associated Proteins metabolism
Mitochondria ultrastructure
Mitochondrial Membranes metabolism
Mitochondrial Proteins genetics
Mitochondrial Proteins metabolism
Nerve Tissue Proteins genetics
Nerve Tissue Proteins metabolism
Proto-Oncogene Proteins c-bcl-2 genetics
Proto-Oncogene Proteins c-bcl-2 metabolism
Reactive Oxygen Species metabolism
Huntington Disease metabolism
Lymphocytes metabolism
Mitochondria metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1539-7262
- Volume :
- 53
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of lipid research
- Publication Type :
- Academic Journal
- Accession number :
- 22773688
- Full Text :
- https://doi.org/10.1194/jlr.M026062