Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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
Doi: 10.1016/j.bbalip.2015.06.005
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Göritzer Madeleine
- Kratky Dagmar
- Radovic Branislav
- Vujic Nemanja
- Co-Autor*innen der Med Uni Graz
- Aflaki Elma
- Chandak Prakash Gopal Das
- Doddapattar Prakash
- Gottschalk Benjamin
- Graier Wolfgang
- Kolb Dagmar
- Korbelius Melanie
- Leopold Christina
- Obrowsky Sascha
- Rainer Silvia
- Sachdev Vinay
- Schlager Stefanie
- Wegscheider Martin
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- 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 (using NLM MeSH Indexing)
- Animals -
- Autophagy - drug effects
- Autophagy - physiology
- Cathepsin B - biosynthesis
- Cathepsin B - genetics
- Enzyme Inhibitors - pharmacology
- Gene Expression Regulation, Enzymologic - drug effects
- Gene Expression Regulation, Enzymologic - physiology
- Lipase - genetics
- Lipase - metabolism
- Lipolysis - drug effects
- Lipolysis - physiology
- Lysosomes - enzymology
- Lysosomes - genetics
- Macrolides - pharmacology
- Macrophages, Peritoneal - cytology
- Macrophages, Peritoneal - metabolism
- Mice -
- Mice, Mutant Strains -
- Sterol Esterase - genetics
- Sterol Esterase - metabolism
- Triglycerides - genetics
- Triglycerides - metabolism
- Find related publications in this database (Keywords)
- Adipose triglyceride lipase
- Hormone-sensitive lipase
- Lipid droplets
- Triglyceride mobilization