Fatty acids are essential for life but are toxic in their free form. Lipid droplets (LDs) are organelles dedicated to storing fatty acids in neutral forms such as triglyceride and cholesteryl esters. Although numerous (patho)physiological circumstances require the extraction of fatty acids from LDs, the mechanisms controlling LD mobilization remain ill-defined. We will address these fundamental unsolved problems in cell biology, focusing on the roles and regulatory mechanisms of autophagic lipid recycling, known as lipophagy, in cellular metabolism and neuronal functions. This regulation has critical implications for human health, and its dysregulation is associated with many diseases, including obesity, fatty liver disease, cancer, and neurological disorders. In particular, deciphering the influence of lipophagy on neuronal lipid metabolism will broaden our knowledge of neuropathology and will enable us to evaluate the lipophagy pathway as a potential therapeutic target for neurodegenerative disorders.
Major projects in the lab will focus on the following questions:
- What are the regulatory mechanisms underlying autophagic lipid recycling?
- How do lipids traffic within the cells and get utilized at inter-organelle membrane contact sites?
- What are the roles of lipophagy in neuronal lipid metabolism and neuropathology?
We employ multidisciplinary approaches encompassing advanced microscopy, biochemistry, and mass spectrometry-based analytics to resolve these longstanding mysteries in the field of lipid metabolism.
Chung J, Park J, Lai ZW, Lambert TJ, Richards RC, Farese RV Jr, Walther TC. (2021) The Troyer syndrome protein spartin mediates selective autophagy of lipid droplets. bioRxiv 2021.08.18.456894. doi:10.1101/2021.08.18.456894.
Chung J, Wu X, Lambert TJ, Lai ZW, Walther TC, Farese RV Jr. (2019) LDAF1 and seipin form a lipid droplet assembly complex. Dev Cell 51: 551–563.e7. PMCID: PMC7235935.
Walther TC, Chung J, Farese RV, Lipid Droplet Biogenesis. (2017) Annu Rev Cell Dev Biol 33: 491-510. PMCID: PMC6986389
Chung J, Torta F, Masai K, Lucast L, Czapla H, Tanner LB, Narayanaswamy P, Wenk MR, Nakatsu F, De Camilli P. (2015) INTRACELLULAR TRANSPORT. PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER-plasma membrane contacts. Science 349: 428–432. PMCID: PMC4638224.
Chung J, Nakatsu F, Baskin JM, De Camilli P. (2015) Plasticity of PI4KIIIα interactions at the plasma membrane. EMBO Rep 16: 312–320. PMCID: PMC4364870.