RRC ID 53304
Author Bar DZ, Charar C, Dorfman J, Yadid T, Tafforeau L, Lafontaine DL, Gruenbaum Y.
Title Cell size and fat content of dietary-restricted Caenorhabditis elegans are regulated by ATX-2, an mTOR repressor.
Journal Proc Natl Acad Sci U S A
Abstract 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 β, 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.
Volume 113(32)
Pages E4620-9
Published 2016-8-9
DOI 10.1073/pnas.1512156113
PII 1512156113
PMID 27457958
PMC PMC4987808
MeSH AMP-Activated Protein Kinases / physiology Adipose Tissue / metabolism* Animals Ataxin-2 / physiology* Caenorhabditis elegans / cytology Caenorhabditis elegans / growth & development* Cell Size* Diet Ribosomal Protein S6 Kinases / physiology Signal Transduction / physiology TOR Serine-Threonine Kinases / physiology*
IF 9.412
Times Cited 20
C.elegans tm3562