Phosphatidylcholine and phosphatidylethanolamine, the two most abundant phospholipids in mammalian cells, are synthesized de novo by the Kennedy pathway from choline and ethanolamine, respectively1–6. Despite the essential roles of these lipids, the mechanisms that enable the cellular uptake of choline and ethanolamine remain unknown. Here we show that the protein encoded by FLVCR1, whose mutation leads to the neurodegenerative syndrome posterior column ataxia and retinitis pigmentosa7–9, transports extracellular choline and ethanolamine into cells for phosphorylation by downstream kinases to initiate the Kennedy pathway. Structures of FLVCR1 in the presence of choline and ethanolamine reveal that both metabolites bind to a common binding site comprising aromatic and polar residues. Despite binding to a common site, FLVCR1 interacts in different ways with the larger quaternary amine of choline in and with the primary amine of ethanolamine. Structure-guided mutagenesis ident
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IMAGE: Mitoribosomes are tethered to the mitochondrial inner membrane to facilitate insertion of synthesized proteins (yellow) encoded by the mitochondrial genome. A gating mechanism of the exit tunnel (cyan) enables protein. view more
Credit: Dan W. Nowakowski and Alexey Amunts
Mitochondria are organelles that act as the powerhouses in our body. They use oxygen which we inhale and food we eat to produce energy that supports our life. This molecular activity is performed by bioenergetic nano-factories incorporated in specialized mitochondrial membranes. The nano-factories consist of proteins cooperatively transporting ions and electrons to generate chemical energy. Those have to be constantly maintained, replaced and duplicated during cell division. To address this, mitochondria have their own bioenergy protein-making machine called the mitoribosome. Given its key role, a deregulation of the mitoribosome can lead to medical disorders such as deafness and diseas