Dissection of surface area-dependent lipolysis at a single organelle level
Chengxin Ma,
Yan Liang,
Xinmeng Che,
Yuqi Li,
Jin Wu,
Li Xu,
Hongyuan Yang,
Tong-Jin Zhao,
Feng-Jung Chen,
Peng Li
Affiliations
Chengxin Ma
Shanghai Key Laboratory of Metabolic Remodeling and Health, State Key Laboratory of Genetics and Development of Complex Phenotypes, Institute of Metabolism and Integrative Biology, School of Life Sciences, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200438, China
Yan Liang
Shanghai Key Laboratory of Metabolic Remodeling and Health, State Key Laboratory of Genetics and Development of Complex Phenotypes, Institute of Metabolism and Integrative Biology, School of Life Sciences, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200438, China
Xinmeng Che
Shanghai Key Laboratory of Metabolic Remodeling and Health, State Key Laboratory of Genetics and Development of Complex Phenotypes, Institute of Metabolism and Integrative Biology, School of Life Sciences, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200438, China
Yuqi Li
State Key Laboratory of Membrane Biology and Tsinghua-Peking Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China
Jin Wu
Shanghai Key Laboratory of Metabolic Remodeling and Health, State Key Laboratory of Genetics and Development of Complex Phenotypes, Institute of Metabolism and Integrative Biology, School of Life Sciences, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200438, China
Li Xu
State Key Laboratory of Membrane Biology and Tsinghua-Peking Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China
Hongyuan Yang
Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; School of Biotechnology and Biomolecular Sciences, the University of New South Wales, Sydney, NSW 2052, Australia
Tong-Jin Zhao
Shanghai Key Laboratory of Metabolic Remodeling and Health, State Key Laboratory of Genetics and Development of Complex Phenotypes, Institute of Metabolism and Integrative Biology, School of Life Sciences, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200438, China; Shanghai Qi Zhi Institute, Shanghai 200030, China
Feng-Jung Chen
Shanghai Key Laboratory of Metabolic Remodeling and Health, State Key Laboratory of Genetics and Development of Complex Phenotypes, Institute of Metabolism and Integrative Biology, School of Life Sciences, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200438, China; Shanghai Qi Zhi Institute, Shanghai 200030, China; Corresponding author
Peng Li
Shanghai Key Laboratory of Metabolic Remodeling and Health, State Key Laboratory of Genetics and Development of Complex Phenotypes, Institute of Metabolism and Integrative Biology, School of Life Sciences, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200438, China; State Key Laboratory of Membrane Biology and Tsinghua-Peking Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; Shanghai Qi Zhi Institute, Shanghai 200030, China; Corresponding author
Summary: Lipid droplets are dynamic organelles whose size and number signify their role in energy. However, owing to cellular heterogeneity and technological limitations, the relationship between the lipolytic ability and lipid droplet morphology is unclear. Here, we developed a live-cell imaging assay using geometric analysis to quantify cellular lipolysis at a single organelle level, designated imaging lipolysis. Using imaging lipolysis and super-resolution imaging, we found that lipolysis is controlled by both lipase-accessible lipid droplet surface area and lipase activity. Moreover, lipid droplet fusion regulatory proteins CLSTN3β/CIDEs promote lipolysis by increasing the total lipid droplet surface area-to-volume ratio in biophysical regulation. We further identified that brown adipocytes exhibit more efficient lipolysis due to higher lipase activity and a larger lipid droplet surface area-to-volume ratio compared to white adipocytes. Taken together, imaging lipolysis generally enabled single-cell lipase activity measurement and revealed a mechanistic basis for energy-generating brown adipocytes to enforce a multilocular phenotype for lipolysis.
