TMEM41B and VMP1 are scramblases and regulate the distribution of cholesterol and phosphatidylserine
Yang E. Li, Yi-Chang Wang, Ximing Du, Tizhong Zhang, Hoi Yin Mak, Sarah E. Hancock, Holly P. McEwen, Elvis Pandžić, Renée Whan, Yvette Celine Aw, Ivan Lukmantara, Yiqiong Yuan, Xiuju Dong, Anthony S. Don, Nigel Turner, Shiqian Qi, Hongyuan Yang
Abstract
TMEM41B and VMP1 are integral membrane proteins of the endoplasmic reticulum (ER) and regulate the formation of autophagosomes, lipid droplets (LDs), and lipoproteins. Recently, TMEM41B was identified as a crucial host factor for infection by all coronaviruses and flaviviruses. The molecular function of TMEM41B and VMP1, which belong to a large evolutionarily conserved family, remains elusive. Here, we show that TMEM41B and VMP1 are phospholipid scramblases whose deficiency impairs the normal cellular distribution of cholesterol and phosphatidylserine. Their mechanism of action on LD formation is likely to be different from that of seipin. Their role in maintaining cellular phosphatidylserine and cholesterol homeostasis may partially explain their requirement for viral infection. Our results suggest that the proper sorting and distribution of cellular lipids are essential for organelle biogenesis and viral infection.