Active autophagy but not lipophagy in macrophages with defective lipolysis.
Bottom Line: We therefore generated mice lacking both ATGL and HSL (A0H0).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.
Affiliation: Institute of Molecular Biology & Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria.Show MeSH
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Mentions: To elucidate the consequences of ATGL and HSL deficiency in macrophages in vivo, we generated A0H0 mice. Genotyping results are shown in Supplemental Fig. S1A; lack of HSL and ATGL in macrophages was confirmed by Western blot analysis (Supplemental Fig. S1B). First we determined TG and CE hydrolase activities in macrophage lysates from Wt, H0, A0, and A0H0 mice. Neutral TG hydrolase activity was significantly decreased in A0 and A0H0 compared with Wt macrophages (51% and 73%, respectively) (Fig. 1A). Neutral CE hydrolase activity was strongly decreased in H0 (88%) and A0H0 (90%) compared with Wt and A0 macrophages (Fig. 1B). These data indicate that the absence of HSL alone markedly contributes to the reduction in neutral CE hydrolase activity, whereas ATGL together with HSL accounts for the main neutral TG hydrolase activities in macrophages.
Affiliation: Institute of Molecular Biology & Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria.