PMID- 27457958
OWN - NLM
STAT- MEDLINE
DCOM- 20180129
LR  - 20240325
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 113
IP  - 32
DP  - 2016 Aug 9
TI  - Cell size and fat content of dietary-restricted Caenorhabditis elegans are 
      regulated by ATX-2, an mTOR repressor.
PG  - E4620-9
LID - 10.1073/pnas.1512156113 [doi]
AB  - Dietary restriction (DR) is a metabolic intervention that extends the lifespan of 
      multiple species, including yeast, flies, nematodes, rodents, and, arguably, 
      rhesus monkeys and humans. Hallmarks of lifelong DR are reductions in body size, 
      fecundity, and fat accumulation, as well as slower development. We have 
      identified atx-2, the Caenorhabditis elegans homolog of the human ATXN2L and 
      ATXN2 genes, as the regulator of these multiple DR phenotypes. Down-regulation of 
      atx-2 increases the body size, cell size, and fat content of dietary-restricted 
      animals and speeds animal development, whereas overexpression of atx-2 is 
      sufficient to reduce the body size and brood size of wild-type animals. atx-2 
      regulates the mechanistic target of rapamycin (mTOR) pathway, downstream of 
      AMP-activated protein kinase (AMPK) and upstream of ribosomal protein S6 kinase 
      and mTOR complex 1 (TORC1), by its direct association with Rab GDP dissociation 
      inhibitor beta, which likely regulates RHEB shuttling between GDP-bound and 
      GTP-bound forms. Taken together, this work identifies a previously unknown 
      mechanism regulating multiple aspects of DR, as well as unknown regulators of the 
      mTOR pathway. They also extend our understanding of diet-dependent growth 
      retardation, and offers a potential mechanism to treat obesity.
FAU - Bar, Daniel Z
AU  - Bar DZ
AUID- ORCID: 0000-0003-4074-2802
AD  - Department of Genetics, Institute of Life Sciences, The Hebrew University of 
      Jerusalem, Givat Ram, Jerusalem 9190401, Israel;
FAU - Charar, Chayki
AU  - Charar C
AD  - Department of Genetics, Institute of Life Sciences, The Hebrew University of 
      Jerusalem, Givat Ram, Jerusalem 9190401, Israel;
FAU - Dorfman, Jehudith
AU  - Dorfman J
AD  - Department of Genetics, Institute of Life Sciences, The Hebrew University of 
      Jerusalem, Givat Ram, Jerusalem 9190401, Israel;
FAU - Yadid, Tam
AU  - Yadid T
AD  - Department of Genetics, Institute of Life Sciences, The Hebrew University of 
      Jerusalem, Givat Ram, Jerusalem 9190401, Israel;
FAU - Tafforeau, Lionel
AU  - Tafforeau L
AD  - RNA Molecular Biology, Fonds de la Recherche Scientifique (F.R.S.-FNRS), Center 
      for Microscopy and Molecular Imaging (CMMI), Universite Libre de Bruxelles (ULB), 
      BioPark Campus, Gosselies B-6041, Belgium.
FAU - Lafontaine, Denis L J
AU  - Lafontaine DL
AUID- ORCID: 0000-0001-7295-6288
AD  - RNA Molecular Biology, Fonds de la Recherche Scientifique (F.R.S.-FNRS), Center 
      for Microscopy and Molecular Imaging (CMMI), Universite Libre de Bruxelles (ULB), 
      BioPark Campus, Gosselies B-6041, Belgium.
FAU - Gruenbaum, Yosef
AU  - Gruenbaum Y
AD  - Department of Genetics, Institute of Life Sciences, The Hebrew University of 
      Jerusalem, Givat Ram, Jerusalem 9190401, Israel; gru@vms.huji.ac.il.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160725
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Ataxin-2)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/physiology
MH  - Adipose Tissue/*metabolism
MH  - Animals
MH  - Ataxin-2/*physiology
MH  - Caenorhabditis elegans/cytology/*growth & development
MH  - *Cell Size
MH  - Diet
MH  - Ribosomal Protein S6 Kinases/physiology
MH  - Signal Transduction/physiology
MH  - TOR Serine-Threonine Kinases/*physiology
PMC - PMC4987808
OTO - NOTNLM
OT  - Caenorhabditis elegans
OT  - TORC1
OT  - mTOR pathway
OT  - metabolism
COIS- The authors declare no conflict of interest.
EDAT- 2016/07/28 06:00
MHDA- 2018/01/30 06:00
PMCR- 2017/02/09
CRDT- 2016/07/27 06:00
PHST- 2016/07/27 06:00 [entrez]
PHST- 2016/07/28 06:00 [pubmed]
PHST- 2018/01/30 06:00 [medline]
PHST- 2017/02/09 00:00 [pmc-release]
AID - 1512156113 [pii]
AID - 201512156 [pii]
AID - 10.1073/pnas.1512156113 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2016 Aug 9;113(32):E4620-9. doi: 
      10.1073/pnas.1512156113. Epub 2016 Jul 25.