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Genotype‐dependent priming to self‐ and xeno‐cannibalism in heterozygous and homozygous lymphoblasts from patients with Huntington's disease
Author(s) -
Mormone Elisabetta,
Matarrese Paola,
Tinari Antonella,
Cannella Milena,
Maglione Vittorio,
Farrace Maria Grazia,
Piacentini Mauro,
Frati Luigi,
Malorni Walter,
Squitieri Ferdinando
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03998.x
Subject(s) - biology , mitochondrion , lymphoblast , programmed cell death , apoptosis , huntington's disease , mitophagy , autophagy , microbiology and biotechnology , phenotype , cell , genetics , cell culture , disease , gene , medicine
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 xeno‐cannibalism. 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 so‐called ‘mitophagy’ and ‘cannibalism’, that only finally lead to cell death.