Sabrina Robichaud (Canada)
University of Ottawa Heart Institute ResearchAuthor Of 2 Presentations
Live Q&A (ID 1550)
O003 - Identification of Novel Lipid Droplet Factors that Regulate Autophagy and Cholesterol Efflux in Macrophage Foam Cells (ID 335)
Abstract
Background and Aims
Macrophage autophagy is a highly anti-atherogenic process that helps maintain cellular homeostasis. In foam cells, autophagy was demonstrated to contribute to the degradation of lipid droplets (LDs) via a selective form of autophagy called lipophagy. Selective autophagy relies on tags such as ubiquitin and selectivity factors to label specific cargo for degradation. Yet, how LDs are targeted for autophagy remains poorly defined. Our study was aimed at identifying LD factors responsible for lipophagy in macrophage foam cells.
Methods
To identify lipophagy factors in macrophage foam cells in an unbiassed manner, we employed mass spectrometry to qualify the LD proteome. Using siRNA array in combination with high-content microscopy and cholesterol efflux screens, we assessed the functional role of these candidate lipophagy factors.
Results
We confirmed the presence of known LD-associated structural and metabolic proteins in the LD proteome. Additionally, we found the association of several proteins related to the ubiquitination machinery and autophagy, along with other novel factors that could regulate lipophagy. We observed that knocking down several of these genes, including Maplc3b and Tfeb significantly reduced cholesterol efflux, suggesting a role for these proteins in lipophagy-mediated LD catabolism. Furthermore, we identified optineurin as a novel cargo receptor for lipophagy.
Conclusions
Our study is the first to systematically identify several LD-associated proteins of the lipophagy machinery, a finding with important biological and therapeutic implications. Therapeutic targeting of these novel lipophagy factors may represent a means to enhance macrophage lipophagy to promote reverse cholesterol transport for the treatment of heart disease.
Presenter of 2 Presentations
Live Q&A (ID 1550)
O003 - Identification of Novel Lipid Droplet Factors that Regulate Autophagy and Cholesterol Efflux in Macrophage Foam Cells (ID 335)
Abstract
Background and Aims
Macrophage autophagy is a highly anti-atherogenic process that helps maintain cellular homeostasis. In foam cells, autophagy was demonstrated to contribute to the degradation of lipid droplets (LDs) via a selective form of autophagy called lipophagy. Selective autophagy relies on tags such as ubiquitin and selectivity factors to label specific cargo for degradation. Yet, how LDs are targeted for autophagy remains poorly defined. Our study was aimed at identifying LD factors responsible for lipophagy in macrophage foam cells.
Methods
To identify lipophagy factors in macrophage foam cells in an unbiassed manner, we employed mass spectrometry to qualify the LD proteome. Using siRNA array in combination with high-content microscopy and cholesterol efflux screens, we assessed the functional role of these candidate lipophagy factors.
Results
We confirmed the presence of known LD-associated structural and metabolic proteins in the LD proteome. Additionally, we found the association of several proteins related to the ubiquitination machinery and autophagy, along with other novel factors that could regulate lipophagy. We observed that knocking down several of these genes, including Maplc3b and Tfeb significantly reduced cholesterol efflux, suggesting a role for these proteins in lipophagy-mediated LD catabolism. Furthermore, we identified optineurin as a novel cargo receptor for lipophagy.
Conclusions
Our study is the first to systematically identify several LD-associated proteins of the lipophagy machinery, a finding with important biological and therapeutic implications. Therapeutic targeting of these novel lipophagy factors may represent a means to enhance macrophage lipophagy to promote reverse cholesterol transport for the treatment of heart disease.