Raft-like microdomains play a key role in mitochondrial impairment in lymphoid cells from patients with Huntington's disease

Journal of Lipid Research

Tina Garofalo¹  Antonella Tinari²  Lucrezia Gambardella³  Walter Malorni³  Valeria Manganelli³  Maurizio Sorice³  Matteo Marconi⁴  Maria Grasso⁵  Paola Matarrese⁵  Laura Ciarlo⁵  Roberta Misasi⁵ 

[1] Center of Integrated Metabolomics, Rome, Italy;and;Department of Experimental Medicine, “Sapienza” University, Rome, Italy;Department of Health, Istituto Superiore di Sanità, Rome, Italy;Section of Cell Aging and Degeneration, Department of Therapeutic Research and Medicine Evaluation, and Department of Technology, Istituto Superiore di Sanità, Rome, Italy;

关键词: rafts;    mitochondria;    fission;    huntingtin;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown