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Cited by 27Mitochondrial Function and PathologyATP Synthase and ATPases ResearchProtein Kinase Regulation and GTPase Signaling

The serum- and glucocorticoid-induced protein kinase-1 (Sgk-1) mitochondria connection: Identification of the IF-1 inhibitor of the F1F0-ATPase as a mitochondria-specific binding target and the stress-induced mitochondrial localization of endogenous Sgk-1

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O'Keeffe, Bridget A., Cilia, Salvatore, Maiyar, Anita C., Vaysberg, Maria, Firestone, Gary L.·2013·Biochimie
DOI 10.1016/j.biochi.2013.01.019PMC PMC3684451
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Abstract

The expression, localization and activity of the serum- and glucocorticoid-induced protein kinase, Sgk-1, are regulated by multiple hormonal and environmental cues including cellular stress. Biochemical fractionation and indirect immunofluorescence demonstrated that sorbitol induced hyperosmotic stress stimulated expression and triggered the localization of endogenous Sgk-1 into the mitochondria of NMuMG mammary epithelial cells. The immunofluorescence pattern of endogenous Sgk-1 was similar to that of a green fluorescent linked fusion protein linked to the N-terminal Sgk-1 fragment that encodes the mitochondrial targeting signal. In the presence or absence of cellular stress, exogenously expressed wild type Sgk-1 efficiently compartmentalized into the mitochondria demonstrating the mitochondrial import machinery per se is not stressed regulated. Co-immunoprecipitation and GST-pull down assays identified the IF-1 mitochondrial matrix inhibitor of the F1F0-ATPase as a new Sgk-1 binding partner, which represents the first observed mitochondrial target of Sgk-1. The Sgk-1/IF-1 interaction requires the 122-176 amino acid region within the catalytic domain of Sgk-1 and is pH dependent, occurring at neutral pH but not at slightly acidic pH, which suggests that this interaction is dependent on mitochondrial integrity. An in vitro protein kinase assay showed that the F1F0-ATPase can be directly phosphorylated by Sgk-1. Taken together, our results suggest that stress-induced Sgk-1 localizes to the mitochondria, which permits access to physiologically appropriate mitochondrial interacting proteins and substrates, such as IF-1 and the F1F0-ATPase, as part of the cellular stressed induced program.

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Cited by

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Authors
O'Keeffe, B. A., Cilia, S., Maiyar, A. C., Vaysberg, M., & Firestone, G. L.
Affiliations
University of California, Berkeley (US)
Venue
Biochimie
Publisher
Elsevier BV
Published
2013-06
Volume
95
Issue
6
Pages
1258-1265
ISSN
  • 0037-9042 (ISSN-L)
  • 0300-9084
DOI
10.1016/j.biochi.2013.01.019
PMC
PMC3684451
OpenAlex
W2014407380
Cited by
27
References
1
Citations by year
2025: 1 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 5 · 2016: 4 · 2015: 1 · 2014: 1
FWCI
0.90
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biochimie (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Health Grant DK-42799 (GLF)
  • NIH
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
SGK1, mitochondria, F1F0-ATPase, hyperosmotic stress, sorbitol, mitochondrial targeting, protein-protein interaction, protein phosphorylation, mitochondrial matrix, mammary epithelial cells, cellular stress response
MeSH terms
ATPase Inhibitory Protein, Serum-Glucocorticoid Regulated Kinases, Animals, Cell Line, Fluorescent Antibody Technique, Proton-Translocating ATPases, Mitochondria, Proteins, Stress, Physiological, Transfection, Blotting, Western, Signal Transduction, Protein Serine-Threonine Kinases, Immediate-Early Proteins, Mice

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