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Mitoguardin-2–mediated lipid transfer preserves mitochondrial morphology and lipid droplet formation

J Cell Biol .. 2022-12; 
Zhouping Hong , Jyoti Adlakha , Neng Wan , Emily Guinn , Fabian Giska , Kallol Gupta , Thomas J Melia , Karin M Reinisch
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Gene Synthesis Human MIGA2 (Uniprot Q7L4E1) gene was codon-optimized for bacterial expression and synthesized by Genescript./The mutant gene fragments were synthesized by Genscript and PCR amplified and cloned into either pCMV10 plasmid with a N-terminal 3xFLAG and a C-terminal 6xhis tag for biochemical experiments, or pLENTi-PGK plasmid (Valverde et al., 2019) or pLVX-CMV plasmid (632159; Get A Quote

摘要

Lipid transport proteins at membrane contacts, where organelles are closely apposed, are critical in redistributing lipids from the endoplasmic reticulum (ER), where they are made, to other cellular membranes. Such protein-mediated transfer is especially important for maintaining organelles disconnected from secretory pathways, like mitochondria. We identify mitoguardin-2, a mitochondrial protein at contacts with the ER and/or lipid droplets (LDs), as a lipid transporter. An x-ray structure shows that the C-terminal domain of mitoguardin-2 has a hydrophobic cavity that binds lipids. Mass spectrometry analysis reveals that both glycerophospholipids and free-fatty acids co-purify with mitoguardin-2 from cells, an... More

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