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TORC1 signaling regulates cytoplasmic pH through Sir2 in yeast.

Authors
  • Devare, Mayur Nimbadas1
  • Kim, Yeong Hyeock1
  • Jung, Joohye1
  • Kang, Woo Kyu1
  • Kwon, Ki-Sun2
  • Kim, Jeong-Yoon1
  • 1 Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon, Korea. , (North Korea)
  • 2 Aging Intervention Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea. , (North Korea)
Type
Published Article
Journal
Aging cell
Publication Date
Jun 01, 2020
Volume
19
Issue
6
Identifiers
DOI: 10.1111/acel.13151
PMID: 32449834
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Glucose controls the phosphorylation of silent information regulator 2 (Sir2), a NAD+ -dependent protein deacetylase, which regulates the expression of the ATP-dependent proton pump Pma1 and replicative lifespan (RLS) in yeast. TORC1 signaling, which is a central regulator of cell growth and lifespan, is regulated by glucose as well as nitrogen sources. In this study, we demonstrate that TORC1 signaling controls Sir2 phosphorylation through casein kinase 2 (CK2) to regulate PMA1 expression and cytoplasmic pH (pHc) in yeast. Inhibition of TORC1 signaling by either TOR1 deletion or rapamycin treatment decreased PMA1 expression, pHc, and vacuolar pH, whereas activation of TORC1 signaling by expressing constitutively active GTR1 (GTR1Q65L) resulted in the opposite phenotypes. Deletion of SIR2 or expression of a phospho-mutant form of SIR2 increased PMA1 expression, pHc, and vacuolar pH in the tor1Δ mutant, suggesting a functional interaction between Sir2 and TORC1 signaling. Furthermore, deletion of TOR1 or KNS1 encoding a LAMMER kinase decreased the phosphorylation level of Sir2, suggesting that TORC1 signaling controls Sir2 phosphorylation. It was also found that Sit4, a protein phosphatase 2A (PP2A)-like phosphatase, and Kns1 are required for TORC1 signaling to regulate PMA1 expression and that TORC1 signaling and the cyclic AMP (cAMP)/protein kinase A (PKA) pathway converge on CK2 to regulate PMA1 expression through Sir2. Taken together, these findings suggest that TORC1 signaling regulates PMA1 expression and pHc through the CK2-Sir2 axis, which is also controlled by cAMP/PKA signaling in yeast. © 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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