Genotype-dependent priming to self- and xeno-cannibalism in heterozygous and homozygous lymphoblasts from patients with Huntington's disease

Elisabetta Mormone, Paola Matarrese, Antonella Tinari, Milena Cannella, Vittorio Maglione, Maria Grazia Farrace, Mauro Piacentini, Luigi Frati, Walter Malorni, Ferdinando Squitieri

Research output: Contribution to journalArticle

Abstract

In the present work, we studied the mitochondrial function and cell death pathway(s) in heterozygous and homozygous immortalized cell lines from patients with Huntington's disease (HD). Heterozygosis was characterized by specific alterations in mitochondrial membrane potential, a constitutive hyperpolarization state of mitochondria, and was correlated with an increased susceptibility to apoptosis. Lymphoblasts from homozygous patients, on the other hand, were characterized by a significant percentage of cells displaying autophagic vacuoles. These cells also demonstrated a striking attitude towards significant cannibalistic activity. Considering the pathogenic role of cell death in HD, our study provides new and useful insights into the role of mitochondrial dysfunction, i.e. hyperpolarization, in hijacking HD heterozygous cells towards apoptosis and HD homozygous cells towards a peculiar phenotype characterized by both self- and xenocannibalism. These events can, however, be viewed as an ultimate attempt to survive rather than a way to die. The present work underlines the possibility that HD-associated mitochondrial defects could tentatively be by-passed by the cells by activating cellular 'phagic' activities, including socalled 'mitophagy' and 'cannibalism', that only finally lead to cell death.

Original languageEnglish
Pages (from-to)1090-1099
Number of pages10
JournalJournal of Neurochemistry
Volume98
Issue number4
DOIs
Publication statusPublished - Aug 2006

Keywords

  • Apoptosis
  • Autophagy
  • Huntington's disease
  • Lymphoblasts
  • Mitochondria

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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