Sar1, a Novel Regulator of ER-Mitochondrial Contact Sites

被引:19
作者
Ackema, Karin B. [1 ]
Prescianotto-Baschong, Cristina [1 ]
Hench, Jurgen [2 ]
Wang, Shyi Chyi [3 ]
Chia, Zhi Hui [3 ]
Mergentaler, Heidi [1 ]
Bard, Frederic [3 ]
Frank, Stephan [2 ]
Spang, Anne [1 ]
机构
[1] Univ Basel, Growth & Dev, Biozentrum, CH-4056 Basel, Switzerland
[2] Univ Basel Hosp, Inst Pathol, Div Neuropathol, CH-4031 Basel, Switzerland
[3] Inst Mol & Cell Biol, Singapore 138673, Singapore
基金
瑞士国家科学基金会;
关键词
EARLY SECRETORY PATHWAY; OUTER-MEMBRANE PROTEIN; SACCHAROMYCES-CEREVISIAE; ENDOPLASMIC-RETICULUM; C-ELEGANS; CAENORHABDITIS-ELEGANS; COPII VESICLE; YEAST; COMPLEX; GTPASE;
D O I
10.1371/journal.pone.0154280
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:16
相关论文
共 48 条
[31]   IDENTIFICATION OF A GENE REQUIRED FOR MEMBRANE-PROTEIN RETENTION IN THE EARLY SECRETORY PATHWAY [J].
NISHIKAWA, S ;
NAKANO, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (17) :8179-8183
[32]   A new mathematical model for relative quantification in real-time RT-PCR [J].
Pfaffl, MW .
NUCLEIC ACIDS RESEARCH, 2001, 29 (09) :E45
[33]   Ordering of compartments in the yeast endocytic pathway [J].
Prescianotto-Baschong, C ;
Riezman, H .
TRAFFIC, 2002, 3 (01) :37-49
[34]   Mutants affecting the structure of the cortical endoplasmic reticulum in Saccharomyces cerevisiae [J].
Prinz, WA ;
Grzyb, L ;
Veenhuis, M ;
Kahana, JA ;
Silver, PA ;
Rapoport, TA .
JOURNAL OF CELL BIOLOGY, 2000, 150 (03) :461-474
[35]   Fzo1p is a mitochondrial outer membrane protein essential for the biogenesis of functional mitochondria in Saccharomyces cerevisiae [J].
Rapaport, D ;
Brunner, M ;
Neupert, W ;
Westermann, B .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (32) :20150-20155
[36]   Golgi structure correlates with transitional endoplasmic reticulum organization in Pichia pastoris and Saccharomyces cerevisiae [J].
Rossanese, OW ;
Soderholm, J ;
Bevis, BJ ;
Sears, IB ;
O'Connor, J ;
Williamson, EK ;
Glick, BS .
JOURNAL OF CELL BIOLOGY, 1999, 145 (01) :69-81
[37]   Concentration of Sec12 at ER exit sites via interaction with cTAGE5 is required for collagen export [J].
Saito, Kota ;
Yamashiro, Koh ;
Shimazu, Noriko ;
Tanabe, Tomoya ;
Kontani, Kenji ;
Katada, Toshiaki .
JOURNAL OF CELL BIOLOGY, 2014, 206 (06) :751-762
[38]   Identification of SEC12, SED4, truncated SEC16, and EKS1/HRD3 as multicopy suppressors of ts mutants of Sar1 GTPase [J].
Saito, Y ;
Yamanushi, T ;
Oka, T ;
Nakano, A .
JOURNAL OF BIOCHEMISTRY, 1999, 125 (01) :130-137
[39]   HIGH-EFFICIENCY TRANSFORMATION OF INTACT YEAST-CELLS USING SINGLE STRANDED NUCLEIC-ACIDS AS A CARRIER [J].
SCHIESTL, RH ;
GIETZ, RD .
CURRENT GENETICS, 1989, 16 (5-6) :339-346
[40]   A Ypt/Rab effector complex containing the Sec1 homolog Vps33p is required for homotypic vacuole fusion [J].
Seals, DF ;
Eitzen, G ;
Margolis, N ;
Wickner, WT ;
Price, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (17) :9402-9407