Presenilin-2 modulation of ER-mitochondria interactions FAD mutations, mechanisms and pathological consequences

• Published in: Communicative & integrative biology Vol. 4; no. 3; pp. 357 - 360
• Main Authors: Zampese, Enrico, Fasolato, Cristina, Pozzan, Tullio, Pizzo, Paola
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01-05-2011; Landes Bioscience
• Subjects: Addendum; Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cycle; Landes; Organogenesis; Proteins; Alzheimer's Disease; Ca2; mitochondria; presenilin; endoplasmic reticulum; organelle juxtaposition
• ISSN: 1942-0889; 1942-0889
• DOI: 10.4161/cib.4.3.15160

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 over-expression, 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.