Active autophagy but not lipophagy in macrophages with defective lipolysis.
Bottom Line: Macrophages from A0H0 mice showed 73% reduced neutral TG hydrolase activity, resulting in TG-rich LD accumulation.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 analyze the autophagic flux we next incubated the macrophages with bafilomycin A1, which inhibits the fusion between autophagosomes and lysosomes, thereby preventing maturation of autophagic vacuoles and degradation of LC3-II and p62. Bafilomycin A1 treatment resulted in comparable increase in LC3-II (Fig. 4A, C) and p62 (Fig. 4B, D) expression in macrophages from Wt, A0, H0, and A0H0 mice with a trend to decreased p62 expression in H0 (Fig. 4B) and A0H0 (Fig. 4D) macrophages. Chloroquine treatment resulted in similarly increased protein expression of LC3-II and p62 in Wt and A0H0 macrophages (Supplemental Fig. 2A, B).
Affiliation: Institute of Molecular Biology & Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria.