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.
Presenilin-2 modulation of ER-mitochondria interactions. FAD mutations, mechanisms and pathological consequences
ZAMPESE, ENRICO;FASOLATO, CRISTINA;POZZAN, TULLIO;PIZZO, PAOLA
2011
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.Pubblicazioni consigliate
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