MIGA2 Links Mitochondria, the ER, and Lipid Droplets and Promotes De Novo Lipogenesis in Adipocytes

• DOI: 10.1016/j.molcel.2019.09.011
• Publication Date: 2019-10-15T14:36:38Z
• Authors: Christophe A.C. F...; Pascal C. Rauher; Christer S. Ejsing; Robin W. Klemm
• Keywords: 0301 basic medicine; Vesicular Transport Proteins; Endoplasmic Reticulum; 1307 Cell Biology; Mitochondrial Proteins; Mice; 03 medical and health sciences; Chlorocebus aethiops; 1312 Molecular Biology; Adipocytes; Animals; Humans; Molecular Biology; adipocyte differentiation; Triglycerides; 0303 health sciences; Lipogenesis; mass spectrometry lipidomics; Membrane Proteins; Cell Differentiation; Cell Biology; lipid droplet expansion; 3T3 Cells; Lipid Droplets; 10124 Institute of Molecular Life Sciences; Mitochondria; HEK293 Cells; organelle contact sites; COS Cells; transcriptomics of adipocyte differentiation; 570 Life sciences; biology

Physical contact between organelles is vital to the function of eukaryotic cells. Lipid droplets (LDs) are dynamic organelles specialized in lipid storage that interact physically with mitochondria in several cell types. The mechanisms coupling these organelles are, however, poorly understood, and the cell-biological function of their interaction remains largely unknown. Here, we discover in adipocytes that the outer mitochondrial membrane protein MIGA2 links mitochondria to LDs. We identify an amphipathic LD-targeting motif and reveal that MIGA2 binds to the membrane proteins VAP-A or VAP-B in the endoplasmic reticulum (ER). We find that in adipocytes MIGA2 is involved in promoting triglyceride (TAG) synthesis from non-lipid precursors. Our data indicate that MIGA2 links reactions of de novo lipogenesis in mitochondria to TAG production in the ER, thereby facilitating efficient lipid storage in LDs. Based on its presence in many tissues, MIGA2 is likely critical for lipid and energy homeostasis in a wide spectrum of cell types.