Biology of Cellular Energy Metabolism

The supply and demand for metabolic energy in cells fluctuates. Therefore, organisms have evolved mechanisms to store metabolic energy. The most efficient way cells store energy is in the form of highly reduced carbons found in triacylglycerols (TGs).

Although energy storage is inherently beneficial, exceeding the capacity for cells to store TGs has led to metabolic diseases such as obesity, diabetes, and fatty liver disease.We study how cells store metabolic energy as TGs in organelles called lipid droplets (LDs). Specifically, we study the molecular basis for how cells synthesize TGs, how cells form LDs, how proteins target to LDs, and how TGs are utilized to meet energetic demands.Our laboratory studies these fundamental questions using a wide range of cutting-edge interdisciplinary approaches, including biophysical, biochemical, and cell biological methods. We also investigate the physiological importance of these lipid storage mechanisms in various cellular and animal models, including models of metabolic diseases or cancer.

Recent Publications:

Song J, Mizrak A, Lee CW, Cicconet M, Lai ZW, Lu CH, Mohr SE, Farese RV Jr**, Walther TC**. (2022). Identification of two pathways mediating protein targeting from ER to lipid droplets. Nat Cell Biol. 24(9):1364-1377.

Arlt H, Sui X, Folger B., Adams C, Chen X, Remme R, Hamprecht F.A, DiMaio F, Liao M, Goodman J.M, Farese RV Jr**, Walther TC**. (2021) Seipin forms a flexible cage at lipid droplet formation sites. Nat Struct Mol Biol. 29(3): 194-202.

Olarte MJ, Kim S, Sharp ME, Swanson JMJ, Farese RV Jr**, Walther TC**. (2020) Determinants of endoplasmic reticulum-to-lipid droplet protein targeting. Dev Cell. 54(4):471-487.e7

Sui X, Wang K, Gluchowski NL, Elliott SD, Liao M, Walther TC**, Farese RV Jr**. (2020) Structure and catalytic mechanism of a human triacylglycerol-synthesis enzyme. Nature. 581(7808):323-328.

Mejhert N, et al. (2020) Partitioning of MLX-Family Transcription Factors to Lipid Droplets Regulates Metabolic Gene Expression. Mol Cell. 77(6):1251-1264.e9.

Gluchowski NL, et al. (2019) Hepatocyte Deletion of Triglyceride-Synthesis Enzyme Acyl CoA: Diacylglycerol Acyltransferase 2 Reduces Steatosis Without Increasing Inflammation or Fibrosis in Mice. Hepatology. 70(6):1972-1985