Type

Journal Article

Authors

Madeline Murphy
Catherine Godson
Finian Martin
Fiona Furlong
Shane Byrne
Darrell Andrews
Helen M. Reid
Heather Mortiboys
Una Bhreathnach
Brenda Griffin
and 2 others

Subjects

Biochemistry

Topics
mitochondrial proteins mitochondria reactive oxygen species diabetic nephropathies metabolism humans oxidative stress proteins transforming growth factor beta1 mitochondrial membrane transport proteins ihg 1 protein human gtp phosphohydrolases energy metabolism genetics signal transduction apoptosis mfn2 protein human fibrosis mfn1 protein human mitochondrial dynamics hela cells cell respiration cell survival

IHG-1 increases mitochondrial fusion and bioenergetic function. (2014)

Abstract Induced in high glucose-1 (IHG-1) is a conserved mitochondrial protein associated with diabetic nephropathy (DN) that amplifies profibrotic transforming growth factor (TGF)-β1 signaling and increases mitochondrial biogenesis. Here we report that inhibition of endogenous IHG-1 expression results in reduced mitochondrial respiratory capacity, ATP production, and mitochondrial fusion. Conversely, overexpression of IHG-1 leads to increased mitochondrial fusion and also protects cells from reactive oxygen species-induced apoptosis. IHG-1 forms complexes with known mediators of mitochondrial fusion-mitofusins (Mfns) 1 and 2-and enhances the GTP-binding capacity of Mfn2, suggesting that IHG-1 acts as a guanine nucleotide exchange factor. IHG-1 must be localized to mitochondria to interact with Mfn1 and Mfn2, and this interaction is necessary for increased IHG-1-mediated mitochondrial fusion. Together, these findings indicate that IHG-1 is a novel regulator of both mitochondrial dynamics and bioenergetic function and contributes to cell survival following oxidant stress. We propose that in diabetic kidney disease increased IHG-1 expression protects cell viability and enhances the actions of TGF-β, leading to renal proximal tubule dedifferentiation, an important event in the pathogenesis of this devastating condition.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Madeline Murphy, Catherine Godson, Finian Martin, Fiona Furlong, Shane Byrne, Darrell Andrews, Helen M. Reid, Heather Mortiboys, Una Bhreathnach, Brenda Griffin and 2 others

Experts in our system

1
Madeline Murphy
University College Dublin
Total Publications: 37
 
2
Catherine Godson
University College Dublin
Total Publications: 93
 
3
Finian Martin
University College Dublin
Total Publications: 81
 
4
Fiona Furlong
University College Dublin
Total Publications: 17
 
5
Helen M. Reid
University College Dublin
Total Publications: 25
 
6
Una Bhreathnach
University College Dublin
Total Publications: 3
 
7
Brenda Griffin
University College Dublin
Total Publications: 5