title: Presenilin-2 modulation of ER-mitochondria interactions: FAD mutations, mechanisms and pathological consequences.
abstract: Presenilin (PS) mutations are the main cause of Familial Alzheimer's Disease (FAD) and have been demonstrated to cause an imbalance of intracellular Ca(2+) homeostasis. Though PS1 and 2 are generally considered to behave similarly in terms of their effects on Ca(2+) handling, we have recently described a novel function, which is unique to PS2, i.e., the modulation of ER-mitochondria juxtaposition. Accordingly, PS2, but not PS1, affects the Ca(2+) cross-talk between these organelles, a key feature in determining cell fate. In particular, PS2 overexpression, and more drastically that of FAD-linked PS2 mutants, strongly increases the interaction between ER and mitochondria, thus facilitating mitochondrial Ca(2+) uptake. The likely mechanisms behind this phenomenon and its potential effects in cell physiology and pathology are discussed.
authors: Department of Biomedical Sciences; University of Padova and CNR Institute of Neuroscience; Padova, Italy.
authors: Enrico
authors: E
authors: Zampese
authors: Cristina
authors: C
authors: Fasolato
authors: Tullio
authors: T
authors: Pozzan
authors: Paola
authors: P
authors: Pizzo