SOD1 integrates signals from oxygen and glucose to repress respiration

Amit R. Reddi, Valeria L Culotta

Research output: Contribution to journalArticle

Abstract

Cu/Zn superoxide dismutase (SOD1) is an abundant enzyme that has been best studied as a regulator of antioxidant defense. Using the yeast Saccharomyces cerevisiae, we report that SOD1 transmits signals from oxygen and glucose to repress respiration. The mechanism involves SOD1-mediated stabilization of two casein kinase 1-gamma (CK1γ) homologs, Yck1p and Yck2p, required for respiratory repression. SOD1 binds a C-terminal degron we identified in Yck1p/Yck2p and promotes kinase stability by catalyzing superoxide conversion to peroxide. The effects of SOD1 on CK1γ stability are also observed with mammalian SOD1 and CK1γ and in a human cell line. Therefore, in a single circuit, oxygen, glucose, and reactive oxygen can repress respiration through SOD1/CK1γ signaling. Our data therefore may provide mechanistic insight into how rapidly proliferating cells and many cancers accomplish glucose-mediated repression of respiration in favor of aerobic glycolysis.

Original languageEnglish (US)
Pages (from-to)224-235
Number of pages12
JournalCell
Volume152
Issue number1-2
DOIs
StatePublished - Jan 7 2013

Fingerprint

Casein Kinase I
Respiration
Oxygen
Glucose
Yeast
Peroxides
Glycolysis
Superoxides
Saccharomyces cerevisiae
Phosphotransferases
Stabilization
Antioxidants
Yeasts
Cells
Cell Line
Networks (circuits)
Enzymes
Neoplasms

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

SOD1 integrates signals from oxygen and glucose to repress respiration. / Reddi, Amit R.; Culotta, Valeria L.

In: Cell, Vol. 152, No. 1-2, 07.01.2013, p. 224-235.

Research output: Contribution to journalArticle

Reddi, Amit R. ; Culotta, Valeria L. / SOD1 integrates signals from oxygen and glucose to repress respiration. In: Cell. 2013 ; Vol. 152, No. 1-2. pp. 224-235.
@article{583bbcd3fb74415d9aa6ec1db88cefb0,
title = "SOD1 integrates signals from oxygen and glucose to repress respiration",
abstract = "Cu/Zn superoxide dismutase (SOD1) is an abundant enzyme that has been best studied as a regulator of antioxidant defense. Using the yeast Saccharomyces cerevisiae, we report that SOD1 transmits signals from oxygen and glucose to repress respiration. The mechanism involves SOD1-mediated stabilization of two casein kinase 1-gamma (CK1γ) homologs, Yck1p and Yck2p, required for respiratory repression. SOD1 binds a C-terminal degron we identified in Yck1p/Yck2p and promotes kinase stability by catalyzing superoxide conversion to peroxide. The effects of SOD1 on CK1γ stability are also observed with mammalian SOD1 and CK1γ and in a human cell line. Therefore, in a single circuit, oxygen, glucose, and reactive oxygen can repress respiration through SOD1/CK1γ signaling. Our data therefore may provide mechanistic insight into how rapidly proliferating cells and many cancers accomplish glucose-mediated repression of respiration in favor of aerobic glycolysis.",
author = "Reddi, {Amit R.} and Culotta, {Valeria L}",
year = "2013",
month = "1",
day = "7",
doi = "10.1016/j.cell.2012.11.046",
language = "English (US)",
volume = "152",
pages = "224--235",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "1-2",

}

TY - JOUR

T1 - SOD1 integrates signals from oxygen and glucose to repress respiration

AU - Reddi, Amit R.

AU - Culotta, Valeria L

PY - 2013/1/7

Y1 - 2013/1/7

N2 - Cu/Zn superoxide dismutase (SOD1) is an abundant enzyme that has been best studied as a regulator of antioxidant defense. Using the yeast Saccharomyces cerevisiae, we report that SOD1 transmits signals from oxygen and glucose to repress respiration. The mechanism involves SOD1-mediated stabilization of two casein kinase 1-gamma (CK1γ) homologs, Yck1p and Yck2p, required for respiratory repression. SOD1 binds a C-terminal degron we identified in Yck1p/Yck2p and promotes kinase stability by catalyzing superoxide conversion to peroxide. The effects of SOD1 on CK1γ stability are also observed with mammalian SOD1 and CK1γ and in a human cell line. Therefore, in a single circuit, oxygen, glucose, and reactive oxygen can repress respiration through SOD1/CK1γ signaling. Our data therefore may provide mechanistic insight into how rapidly proliferating cells and many cancers accomplish glucose-mediated repression of respiration in favor of aerobic glycolysis.

AB - Cu/Zn superoxide dismutase (SOD1) is an abundant enzyme that has been best studied as a regulator of antioxidant defense. Using the yeast Saccharomyces cerevisiae, we report that SOD1 transmits signals from oxygen and glucose to repress respiration. The mechanism involves SOD1-mediated stabilization of two casein kinase 1-gamma (CK1γ) homologs, Yck1p and Yck2p, required for respiratory repression. SOD1 binds a C-terminal degron we identified in Yck1p/Yck2p and promotes kinase stability by catalyzing superoxide conversion to peroxide. The effects of SOD1 on CK1γ stability are also observed with mammalian SOD1 and CK1γ and in a human cell line. Therefore, in a single circuit, oxygen, glucose, and reactive oxygen can repress respiration through SOD1/CK1γ signaling. Our data therefore may provide mechanistic insight into how rapidly proliferating cells and many cancers accomplish glucose-mediated repression of respiration in favor of aerobic glycolysis.

UR - http://www.scopus.com/inward/record.url?scp=84872550003&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872550003&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2012.11.046

DO - 10.1016/j.cell.2012.11.046

M3 - Article

C2 - 23332757

AN - SCOPUS:84872550003

VL - 152

SP - 224

EP - 235

JO - Cell

JF - Cell

SN - 0092-8674

IS - 1-2

ER -