Type

Journal Article

Authors

Madeline Murphy
Debra Higgins
Leah Ewart
Eoin Brennan
Brenda Griffin
Una Bhreathnach

Subjects

Biochemistry

Topics
oxidative stress chronic kidney disease mass spectrometry 1 protein dna repair ureteral obstruction renal disease reactive oxygen species

Profibrotic IHG-1 complexes with renal disease associated HSPA5 and TRAP1 in mitochondria. (2016)

Abstract The highly conserved mitochondrial protein induced in high glucose-1 (IHG-1) functions to maintain mitochondrial quality and is associated with the development of fibrosis in diabetic nephropathy. Towards identifying novel approaches to treating diabetic kidney disease, IHG-1-protein-protein interactions were investigated using epitope-tagged immunoprecipitation analyses followed by mass spectrometry. Here we show that IHG-1 is solely expressed in mitochondria and localised to the inner mitochondrial membrane, the region where mitochondrial reactive oxygen species are generated. Chaperones HSPA5 and TRAP1 and cold shock protein YBX1 were identified as IHG-1 binding partners. All three proteins are important in the cellular response to oxidative stress and play important roles in mitochondrial transcription and DNA repair. Both redox imbalance and IHG-1 stimulate TGF-β signalling. IHG-1, HSPA5 and YBX1 all show increased expression in diabetic nephropathy, chronic kidney disease and in the Unilateral Ureteral Obstruction model of kidney fibrosis. Increased IHG-1 expression in UUO correlated with loss of TRAP1 expression. IHG-1 may target TRAP1 for degradation. When IHG-1 is no longer localised to mitochondria, it retains the ability to interact with the cold shock protein YBX1, facilitating anti-fibrotic actions in the nucleus. Targeting these proteins may offer alternative treatments for fibrotic kidney disease.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Madeline Murphy, Debra Higgins, Leah Ewart, Eoin Brennan, Brenda Griffin, Una Bhreathnach

Experts in our system

1
Madeline Murphy
University College Dublin
Total Publications: 37
 
2
Debra F Higgins
University College Dublin
Total Publications: 11
 
3
Eoin P Brennan
University College Dublin
Total Publications: 18
 
4
Brenda Griffin
University College Dublin
Total Publications: 5
 
5
Una Bhreathnach
University College Dublin
Total Publications: 3