Sar1, a Novel Regulator of ER-Mitochondrial Contact Sites

• Published in: PloS one 2016-04, Vol.11 (4), p.e0154280-e0154280
• Main Authors: Ackema, Karin B, Prescianotto-Baschong, Cristina, Hench, Jürgen, Wang, Shyi Chyi, Chia, Zhi Hui, Mergentaler, Heidi, Bard, Fredéric, Frank, Stephan, Spang, Anne
• Format: Article
• Language: English
• Subjects: Amino Acid Substitution; Animals; Biology; Biology and Life Sciences; Biosynthesis; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - antagonists & inhibitors; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cleavage; Conserved Sequence; Curvature; Dynamin; Dynamins - genetics; Dynamins - metabolism; Endoplasmic reticulum; Endoplasmic Reticulum - chemistry; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum - ultrastructure; Gene expression; Gene Expression Regulation; Genetic aspects; Glycerol; GTP Phosphohydrolases - antagonists & inhibitors; GTP Phosphohydrolases - genetics; GTP Phosphohydrolases - metabolism; Guanosine triphosphatases; HeLa Cells; Humans; Intracellular Membranes - chemistry; Intracellular Membranes - metabolism; Ion Transport; Lipid Metabolism; Lipids; Medicine and Health Sciences; Mitochondria; Mitochondria - chemistry; Mitochondria - metabolism; Mitochondria - ultrastructure; Mitochondrial Dynamics; Monomeric GTP-Binding Proteins - antagonists & inhibitors; Monomeric GTP-Binding Proteins - genetics; Monomeric GTP-Binding Proteins - metabolism; Morphology; Mutation; Nematodes; Neuropathology; Organelles; Physiological aspects; Proteins; Research and Analysis Methods; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae - ultrastructure; Saccharomyces cerevisiae Proteins - antagonists & inhibitors; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Signal Transduction; Temperature; Tubules; Vesicular Transport Proteins - antagonists & inhibitors; Vesicular Transport Proteins - genetics; Vesicular Transport Proteins - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0154280

Endoplasmic reticulum (ER)-mitochondrial contact sites play a pivotal role in exchange of lipids and ions between the two organelles. How size and function of these contact sites are regulated remains elusive. Here we report a previously unanticipated, but conserved role of the small GTPase Sar1 in the regulation of ER-mitochondrial contact site size. Activated Sar1 introduces membrane curvature through its N-terminal amphiphatic helix at the ER-mitochondria interphase and thereby reducing contact size. Conversely, the S. cerevisiae N3-Sar1 mutant, in which curvature induction is decreased, caused an increase in ER-mitochondrial contacts. As a consequence, ER tubules are no longer able to mark the prospective scission site on mitochondria, thereby impairing mitochondrial dynamics. Consistently, blocking mitochondrial fusion partially rescued, whereas deletion of the dynamin-like protein enhanced the phenotype in the sar1D32G mutant. We conclude that Sar1 regulates the size of ER-mitochondria contact sites through its effects on membrane curvature.