Targeted Lipidomics of Mitochondria in a Cellular Alzheimer’s Disease Model

Biomedicines

Veronika Matschke¹  Tobias Hartmann²  Jakob Winkler³  Elena Leoni Theiss³  Sabrina Melanie Pilz³  Marcus Otto Walter Grimm³  Anna Andrea Lauer³  Heike Sabine Grimm³  Irina Kurokin³  Daniel Janitschke³  Lea Victoria Griebsch³  Martin van der Laan⁴ 

[1] Department of Cytology, Institute of Anatomy, Medical Faculty, Ruhr University Bochum, D-44801 Bochum, Germany;Deutsches Institut für Demenzprävention, Saarland University, 66421 Homburg, Germany;Experimental Neurology, Saarland University, 66421 Homburg, Germany;Medical Biochemistry & Molecular Biology, Center for Molecular Signaling PZMS, Saarland University Medical School, 66421 Homburg, Germany;

关键词: mitochondria;    Alzheimer’s disease;    neurodegeneration;    lipidomics;    unsaturated fatty acids;    phosphatidylcholine;   

DOI  :  10.3390/biomedicines9081062

来源: DOAJ

【 摘 要 】

Alzheimer’s disease (AD) is neuropathologically characterized by the accumulation of Amyloid-β (Aβ) in senile plaques derived from amyloidogenic processing of a precursor protein (APP). Recently, changes in mitochondrial function have become in the focus of the disease. Whereas a link between AD and lipid-homeostasis exists, little is known about potential alterations in the lipid composition of mitochondria. Here, we investigate potential changes in the main mitochondrial phospholipid classes phosphatidylcholine, phosphatidylethanolamine and the corresponding plasmalogens and lyso-phospholipids of a cellular AD-model (SH-SY5Y APPswedish transfected cells), comparing these results with changes in cell-homogenates. Targeted shotgun-lipidomics revealed lipid alterations to be specific for mitochondria and cannot be predicted from total cell analysis. In particular, lipids containing three and four times unsaturated fatty acids (FA X:4), such as arachidonic-acid, are increased, whereas FA X:6 or X:5, such as eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), are decreased. Additionally, PE plasmalogens are increased in contrast to homogenates. Results were confirmed in another cellular AD model, having a lower affinity to amyloidogenic APP processing. Besides several similarities, differences in particular in PE species exist, demonstrating that differences in APP processing might lead to specific changes in lipid homeostasis in mitochondria. Importantly, the observed lipid alterations are accompanied by changes in the carnitine carrier system, also suggesting an altered mitochondrial functionality.

【 授权许可】

Unknown