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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Goeritzer, M; Vujic, N; Schlager, S; Chandak, PG; Korbelius, M; Gottschalk, B; Leopold, C; Obrowsky, S; Rainer, S; Doddapattar, P; Aflaki, E; Wegscheider, M; Sachdev, V; Graier, WF; Kolb, D; Radovic, B; Kratky, D.
Active autophagy but not lipophagy in macrophages with defective lipolysis.
Biochim Biophys Acta. 2015; 1851(10): 1304-1316. [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Aflaki Elma
Chandak Prakash Gopal Das
Doddapattar Prakash
Göritzer Madeleine
Gottschalk Benjamin
Graier Wolfgang
Kolb-Lenz Dagmar
Korbelius Melanie
Kratky Dagmar
Leopold Christina
Obrowsky Sascha
Radovic Branislav
Rainer Silvia
Sachdev Vinay
Schlager Stefanie
Vujic Nemanja
Wegscheider Martin
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Number of Figures: 9
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Abstract:
During autophagy, autophagosomes fuse with lysosomes to degrade damaged organelles and misfolded proteins. Breakdown products are released into the cytosol and contribute to energy and metabolic building block supply, especially during starvation. Lipophagy has been defined as the autophagy-mediated degradation of lipid droplets (LDs) by lysosomal acid lipase. Adipose triglyceride lipase (ATGL) is the major enzyme catalyzing the initial step of lipolysis by hydrolyzing triglycerides (TGs) in cytosolic LDs. Consequently, most organs and cells, including macrophages, lacking ATGL accumulate TGs, resulting in reduced intracellular free fatty acid concentrations. Macrophages deficient in hormone-sensitive lipase (H0) lack TG accumulation albeit reduced in vitro TG hydrolase activity. We hypothesized that autophagy is activated in lipase-deficient macrophages to counteract their energy deficit. We therefore generated mice lacking both ATGL and HSL (A0H0). Macrophages from A0H0 mice showed 73% reduced neutral TG hydrolase activity, resulting in TG-rich LD accumulation. Increased expression of cathepsin B, accumulation of LC3-II, reduced expression of p62 and increased DQ-BSA dequenching suggest intact autophagy and functional lysosomes in A0H0 macrophages. Markedly decreased acid TG hydrolase activity and lipid flux independent of bafilomycin A1 treatment, however, argue against effective lysosomal degradation of LDs in A0H0 macrophages. We conclude that autophagy of proteins and cell organelles but not of LDs is active as a compensatory mechanism to circumvent and balance the reduced availability of energy substrates in A0H0 macrophages. Copyright © 2015. Published by Elsevier B.V.

Find related publications in this database (Keywords)
Adipose triglyceride lipase
Hormone-sensitive lipase
Lipid droplets
Triglyceride mobilization
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