Hello from the other side: Membrane contact of lipid droplets with other organelles and subsequent functional implications

Lipid droplets (LDs) are ubiquitous organelles that play crucial roles in response to physiological and environmental cues. The identification of several neutral lipid synthesizing and regulatory protein complexes have propelled significant advance on the mechanisms of LD biogenesis in the endoplasmic reticulum (ER). Increasing evidence suggests that distinct proteins and regulatory factors, which localize to membrane contact sites (MCS), are involved not only in interorganellar lipid exchange and transport, but also function in other important cellular processes, including autophagy, mitochondrial dynamics and inheritance, ion signaling and inter-regulation of these MCS. More and more tethers and molecular determinants are associated to MCS and to a diversity of cellular and pathophysiological processes, demonstrating the dynamics and importance of these junctions in health and disease. The conjugation of lipids with proteins in supramolecular complexes is known to be paramount for many biological processes, namely membrane biosynthesis, cell homeostasis, regulation of organelle division and biogenesis, and cell growth. Ultimately, this physical organization allows the contact sites to function as crucial metabolic hubs that control the occurrence of chemical reactions. This leads to biochemical and metabolite compartmentalization for the purposes of energetic efficiency and cellular homeostasis. In this review, we will focus on the structural and functional aspects of LD-organelle interactions and how they ensure signaling exchange and metabolites transfer between organelles.