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

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ABSTRACT
Huntington’s disease (HD) is a genetic neurodegenerative disease due to an exceedingly high  number of contiguous glutamine residues in the translated protein, huntingtin. 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. Drp1, as well as huntingtin, 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 mitochondria remodeling in HD cells, suggest that  mitochondrial alterations occurring in these cells could be due to raft-mediated defects of  mitochondrial fission/fusion machinery.

 

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