Mapping the lipidome in mitochondria ‐associated membranes (MAMs) in an in vitro model of Alzheimer's disease

The accumulation of APP and A β that occurs in N2A APPswe cells (AD cell model), which is known to change the communication between the ER and mitochondria affecting interorganelle Ca2+ transfer and ATP production, also affects the lipid homeostasis in the ER, MAMs, and mitochondria. A differential phospholipids and fatty acids species profile is observed in the membranes of these organelles and subcellular inter-organelle structures, indicating the specificity of each lipidome. The AD-associated lipid changes can represent an attempt to adjust to stressful and pathological conditions. AbstractThe disruption of mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) plays a relevant role in Alzheimer's disease (AD). MAMs have been implicated in neuronal dysfunction and death since it is associated with impairment of functions regulated in this subcellular domain, including lipid synthesis and trafficking, mitochondria dysfunction, ER stress-induced unfolded protein response (UPR), apoptosis, and inflammation. Since MAMs play an important role in lipid metabolism, in this study we characterized and investigated the lipidome alterations at MAMs in comparison with other subcellular fractions, namely microsomes and mitochondria, using an in  vitro model of AD, namely the mouse neuroblastoma cell line (N2A) over-expressing the APP familial Swedish mutation (APPswe) and the respective control (WT) cells. Phospholipids (PLs) and fatty acids (FAs) were isolated from the...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research