Lipid transport is an essential process that underlies the biogenesis and expansion of organelles. Despite its basic importance, there is a dearth of assays to probe lipid exchange between organelles in vivo. Here we discuss the development of a versatile method called METALIC (Mass tagging-Enabled Tracking of Lipids in Cells), that uses enzyme-based mass tagging of lipids in conjunction with mass spectrometry to track interorganelle lipid transport inside living cells.

Lipid trafficking is critical for the biogenesis and expansion of organelle membranes. Lipid transport proteins (LTPs) have been proposed to facilitate lipid transport at contact sites between organelles. Despite the fundamental importance of LTPs in cell physiology, our knowledge on the mechanisms of interorganelle lipid distribution remains poor due to the scarcity of assays to monitor lipid flux in vivo. In this review, we highlight the recent development of a versatile method named METALIC (Mass tagging-Enabled Tracking of Lipids in Cells), which uses a combination of enzymatic mass tagging and mass spectrometry to track lipid flux between organelles inside living cells. We discuss the methodology, its distinct advantages, limitations as well as its potential to unearth the pipelines of lipid transport and LTP function in vivo.