The architecture of the endoplasmic reticulum (ER) consists of an intricate network of sheets and tubules, but how these domains are generated remains largely unknown. The reticulons and reticulon-like proteins are needed to shape the ER. Surprisingly, yeast missing all these proteins are viable and have few phenotypes. To better understand the role of ER-shaping proteins we screened for mutations that cause cells that lack the reticulons to grow poorly. We found that cells lacking the reticulons grow poorly if they are also missing a complex of proteins that tethers the ER and mitochondria. Close contacts between the ER and mitochondria are necessary for efficient lipid exchange between these organelles and mitochondrial biogenesis. We found the phospholipid exchange between the ER and mitochondria slows in cells missing the reticulons and the ER-mitochondria tethering complex. These findings suggest that reticulons are necessary to maintain functional ER-mitochondria contacts. This work is being prepared for submission. In a second project we are working on the role a dynamin-like GTPase called Sey1 in ER-ER fusion and ER biogenesis. We have found that ER-ER fusion slows dramatically in cells missing Sey1 and that Sey1 can mediate fusion of liposomes. Surprisingly, homotypic ER fusion still occurs in cells missing Sey1, suggesting that there is a second fusion pathway. We have evidence that this pathway requires ER SNARE proteins. This work has been submitted for publication. The third project is to identify proteins required to form regions of close apposition between the ER and other membranes in the cell, often called membrane contact sites (MCSs).

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Lin, Cheng-Chao; Kurashige, Mahiro; Liu, Yi et al. (2018) A cleavage product of Polycystin-1 is a mitochondrial matrix protein that affects mitochondria morphology and function when heterologously expressed. Sci Rep 8:2743
Joshi, Amit S; Nebenfuehr, Benjamin; Choudhary, Vineet et al. (2018) Lipid droplet and peroxisome biogenesis occur at the same ER subdomains. Nat Commun 9:2940
Liu, Li-Ka; Choudhary, Vineet; Toulmay, Alexandre et al. (2017) An inducible ER-Golgi tether facilitates ceramide transport to alleviate lipotoxicity. J Cell Biol 216:131-147
Michaud, Morgane; Prinz, William A; Jouhet, Juliette (2017) Glycerolipid synthesis and lipid trafficking in plant mitochondria. FEBS J 284:376-390
Kannan, Muthukumar; Lahiri, Sujoy; Liu, Li-Ka et al. (2017) Phosphatidylserine synthesis at membrane contact sites promotes its transport out of the ER. J Lipid Res 58:553-562
Joshi, Amit S; Zhang, Hong; Prinz, William A (2017) Organelle biogenesis in the endoplasmic reticulum. Nat Cell Biol 19:876-882
Murley, Andrew; Yamada, Justin; Niles, Bradley J et al. (2017) Sterol transporters at membrane contact sites regulate TORC1 and TORC2 signaling. J Cell Biol 216:2679-2689
Michaud, Morgane; Gros, Valérie; Tardif, Marianne et al. (2016) AtMic60 Is Involved in Plant Mitochondria Lipid Trafficking and Is Part of a Large Complex. Curr Biol 26:627-39
Kannan, Muthukumar; Sivaprakasam, Chinnarasu; Prinz, William A et al. (2016) Endoplasmic reticulum stress affects the transport of phosphatidylethanolamine from mitochondria to the endoplasmic reticulum in S.cerevisiae. Biochim Biophys Acta 1861:1959-1967
Choudhary, Vineet; Golden, Andy; Prinz, William A (2016) Keeping FIT, storing fat: Lipid droplet biogenesis. Worm 5:e1170276

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