Egea Lab Publishes Paper in PNAS

Egea Lab Publishes Paper in PNAS

Andrew Ah Young, a graduate student in Pascal Egea's lab published a paper in Proceedings of the National Academy of Sciences.

Membrane-bound organelles form highly dynamic and interconnected networks. This complexity makes a permanent crosstalk between the organelles a necessity for the coordination of cellular functions. This fundamental aspect of eukaryotic cell biology has attracted a lot of interest in the past few years. The tight juxtaposition of membranes from different types of organelles is essential to the controlled exchanges of matter and information within cells and is mediated by various organelle-tethering protein complexes. Small metabolites and messengers such as phospholipids and calcium ions are exchanged at these membrane contact sites between organelles. Phospholipid exchange between the endoplasmic reticulum (ER) and mitochondria is essential for membrane biogenesis and, ultimately, cell survival. It remains unclear, however, how this exchange is facilitated.

In this collaborative study, Ah Young et al. investigate a putative involvement of the ER-mitochondrial encounter structure (ERMES), a tethering complex that bridges the ER and mitochondria, in phospholipid transport in yeast. We show that a conserved ERMES domain called the “synaptotagmin-like mitochondrial lipid-binding protein” (SMP) domain preferentially binds phosphatidylcholines and mediates the hierarchical assembly of the tether. The 17-Å-resolution EM structure of the complex formed between the SMP domains present in two ERMES subunits, Mdm12 and Mmm1, reveals an elongated, tubular-shaped heterotetramer traversed by a hydrophobic channel, suggesting a mechanism for lipid transport between the two organelles.

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