title: Raft-like microdomains play a key role in mitochondrial impairment in lymphoid cells from patients with Huntington's disease.
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.
authors: Section of Cell Aging and Degeneration, Department of Therapeutic Research and Medicine Evaluation, and Department of Technology, Istituto Superiore di Sanità, Rome, Italy.
authors: Laura
authors: L
authors: Ciarlo
authors: Department of Experimental Medicine, "Sapienza" University, Rome, Italy.
authors: Valeria
authors: V
authors: Manganelli
authors: Section of Cell Aging and Degeneration, Department of Therapeutic Research and Medicine Evaluation, and Department of Technology, Istituto Superiore di Sanità, Rome, Italy; Center of Integrated Metabolomics, Rome, Italy; and.
authors: Paola
authors: P
authors: Matarrese
authors: Department of Experimental Medicine, "Sapienza" University, Rome, Italy.
authors: Tina
authors: T
authors: Garofalo
authors: Department of Health, Istituto Superiore di Sanità, Rome, Italy.
authors: Antonella
authors: A
authors: Tinari
authors: Section of Cell Aging and Degeneration, Department of Therapeutic Research and Medicine Evaluation, and Department of Technology, Istituto Superiore di Sanità, Rome, Italy.
authors: Lucrezia
authors: L
authors: Gambardella
authors: Section of Cell Aging and Degeneration, Department of Therapeutic Research and Medicine Evaluation, and Department of Technology, Istituto Superiore di Sanità, Rome, Italy.
authors: Matteo
authors: M
authors: Marconi
authors: Department of Experimental Medicine, "Sapienza" University, Rome, Italy.
authors: Maria
authors: M
authors: Grasso
authors: Department of Experimental Medicine, "Sapienza" University, Rome, Italy.
authors: Roberta
authors: R
authors: Misasi
authors: Department of Experimental Medicine, "Sapienza" University, Rome, Italy.
authors: Maurizio
authors: M
authors: Sorice
authors: Section of Cell Aging and Degeneration, Department of Therapeutic Research and Medicine Evaluation, and Department of Technology, Istituto Superiore di Sanità, Rome, Italy; San Raffaele Institute Sulmona, L'Aquila, Italy. Electronic address: malorni@iss.it.
authors: Walter
authors: W
authors: Malorni
mesh_terms: D017209:Apoptosis; D034281:Dynamins; D005455:Fluorescent Antibody Technique; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D016253:Microscopy, Immunoelectron; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D009419:Nerve Tissue Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins