Identification of Novel Lipid Droplet Factors that Regulate Lipophagy and Cholesterol Efflux in Macrophage Foam Cells

Macrophage autophagy is a highly anti-atherogenic process that promotes the catabolism of cytosolic lipid droplets (LDs) to maintain cellular lipid homeostasis. Selective autophagy relies on tags such as ubiquitin and a set of selectivity factors including selective autophagy receptors (SARs) to label specific cargo for degradation. Originally described in yeast cells, ‘lipophagy’ refers to the degradation of LDs by autophagy. Yet, how LDs are targeted for autophagy is poorly defined. Here, we employed mass spectrometry to identify lipophagy factors within the macrophage foam cell LD proteome. In addition to structural proteins (e.g. PLIN2), metabolic enzymes (e.g. ACSL) and neutral lipases (e.g. PLPL2), we found the association of proteins related to the ubiquitination machinery (e.g. AUP1) and autophagy (e.g. HMGB, 1433).