Sar1, a Novel Regulator of ER-Mitochondrial Contact Sites.
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.
Growth and Development, Biozentrum, University of Basel, 4056 Basel, Switzerland.
Karin B
KB
Ackema
Growth and Development, Biozentrum, University of Basel, 4056 Basel, Switzerland.
Cristina
C
Prescianotto-Baschong
Division of Neuropathology, Institute of Pathology, University Hospital Basel, 4031 Basel, Switzerland.
Jürgen
J
Hench
Institute for Molecular and Cell Biology, Singapore 138673, Singapore.
Shyi Chyi
SC
Wang
Institute for Molecular and Cell Biology, Singapore 138673, Singapore.
Zhi Hui
ZH
Chia
Growth and Development, Biozentrum, University of Basel, 4056 Basel, Switzerland.
Heidi
H
Mergentaler
Institute for Molecular and Cell Biology, Singapore 138673, Singapore.
Fredéric
F
Bard
Division of Neuropathology, Institute of Pathology, University Hospital Basel, 4031 Basel, Switzerland.
Stephan
S
Frank
Growth and Development, Biozentrum, University of Basel, 4056 Basel, Switzerland.
Anne
0000-0002-2387-6203
A
Spang
D019943:Amino Acid Substitution; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D017124:Conserved Sequence; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry / Q000378:metabolism; D017136:Ion Transport; D050356:Lipid Metabolism; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D063154:Mitochondrial Dynamics; D020559:Monomeric GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D034741:RNA, Small Interfering; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; D020558:GTP Phosphohydrolases; C000607940:SAR-1 protein, C elegans; C493083:SAR1A protein, human; D020559:Monomeric GTP-Binding Proteins; C077395:SAR1 protein, S cerevisiae; D034281:Dynamins; C568498:dynamin-related protein 1, C elegans