Speaker: Professor Chen Xiaowei, College of Future Technology, PKU
Time: 10:00-11:30 a.m., November 17, 2023, GMT+8
Venue: B101, Lui Che-woo Building
Precise control of circulating lipids is instrumental in health and disease.Bulk lipids, carried by specialized lipoproteins, are secreted into the circulation initially via the COPII complex. How the universal COPII machinery accommodates the abundant yet unconventional lipoproteins remains unclear, let alone its therapeutic translation. We recently discovered that COPII employs manganese-tuning, self-constrained condensation to selectively drive lipoprotein delivery and set lipid homeostasis in vivo. Serendipitously, adenovirus hijacks the condensation-based transport mechanism, thus enabling the identification of cytosolic manganese as an unexpected control signal. Manganese directly binds the inner COPII coat and enhances its condensation, thereby shifting the assembly-vs-dynamics balance of the transport machinery. Manganese can be mobilized from mitochondria stores to signal COPII and selectively controls lipoprotein secretion with a distinctive, bell-shape function. Consequently, dietary titration of manganese enables tailored lipid management that counters pathological dyslipidemia and enables the reversal of existing atherosclerotic plagues, implicating a condensation-targeting strategy with broad therapeutic potential for cardio-metabolic health.
Source: School of Life Sciences, PKU