title: Genotype-dependent priming to self- and xeno-cannibalism in heterozygous and homozygous lymphoblasts from patients with Huntington's disease.
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 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.
authors.affiliation: Department of Drug Research and Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Mormone
authors.forename: Paola
authors.initials: P
authors.lastname: Matarrese
authors.forename: Antonella
authors.initials: A
authors.lastname: Tinari
authors.forename: Milena
authors.initials: M
authors.lastname: Cannella
authors.forename: Vittorio
authors.initials: V
authors.lastname: Maglione
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Farrace
authors.forename: Mauro
authors.initials: M
authors.lastname: Piacentini
authors.forename: Luigi
authors.initials: L
authors.lastname: Frati
authors.forename: Walter
authors.initials: W
authors.lastname: Malorni
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Squitieri
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D005434:Flow Cytometry; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006816:Huntington Disease / Q000235:genetics* / Q000473:pathology*; D008214:Lymphocytes / Q000276:immunology*; D008564:Membrane Potentials / Q000502:physiology; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D010587:Phagocytosis / Q000235:genetics*
chemical_list: D017304:Annexin A5