James B. Corcoran

University College Dublin

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Catherine Godson

University College Dublin

Madeline Murphy

University College Dublin

Finian Martin

University College Dublin

Fiona Furlong

Queen's University Belfast

ÚB

Úna Bhreathnach

St. James's Hospital

Fionnuala B. Hickey

Trinity College Dublin

Brenda Walker Griffin

St. James's Hospital

Heather Mortiboys

University of Sheffield

Helen M. Reid

University College Dublin

Darrell Andrews

University College Dublin

Cooperative Institutions

University College Dublin

Mater Misericordiae University Hospital

Conway School of Landscape Design

Health Research Board

Molecular Medicine Ireland

Ludwig-Maximilians-Universität München

Trinity College Dublin

St. Vincent's University Hospital

Austral University of Chile

Sahlgrenska University Hospital

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

IHG-1 Promotes Mitochondrial Biogenesis by Stabilizing PGC-1α

Journal of the American Society of Nephrology (2011)

Fionnuala B. Hickey James B. Corcoran Neil G. Docherty Brenda Walker Griffin Úna Bhreathnach

Increased expression of Induced-by-High-Glucose 1 (IHG-1) associates with tubulointerstitial fibrosis in diabetic nephropathy. IHG-1 amplifies TGF-β1 signaling, but the functions of this highly-conserved protein are not well understood. IHG-1 contains a putative mitochondrial-localization domain, and here we report that IHG-1 is specifically localized to mitochondria. IHG-1 overexpression increased mitochondrial mass and stabilized peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). Conversely, inhibition of IHG-1 expression decreased mitochondrial mass, downregulated mitochondrial proteins, and PGC-1α-regulated transcription factors, including nuclear respiratory factor 1 and mitochondrial transcription factor A (TFAM), and reduced activity of the TFAM promoter. In the unilateral ureteral obstruction model, we observed higher PGC-1α protein expression and IHG-1 levels with fibrosis. In a gene-expression database, we noted that renal biopsies of human diabetic nephropathy demonstrated higher expression of genes encoding key mitochondrial proteins, including cytochrome c and manganese superoxide dismutase, compared with control biopsies. In summary, these data suggest that IHG-1 increases mitochondrial biogenesis by promoting PGC-1α-dependent processes, potentially contributing to the pathogenesis of renal fibrosis.

TFAM

NRF1

10.1681/asn.2010111154

Cite

Citations (38)

IHG-1 Increases Mitochondrial Fusion and Bioenergetic Function

Diabetes (2014)

Fionnuala B. Hickey James B. Corcoran Brenda Walker Griffin Úna Bhreathnach Heather Mortiboys

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.

MFN2

MFN1

DNAJA3

Bioenergetics

10.2337/db13-1256

Cite

Citations (18)

IHG-1 must be localised to mitochondria to decrease Smad7 expression and amplify TGF-β1-induced fibrotic responses

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research (2013)

James B. Corcoran Sarah McCarthy Brenda Walker Griffin Andrew Gaffney Úna Bhreathnach

R-SMAD

10.1016/j.bbamcr.2013.03.027

Cite

Citations (20)

IHG-1 Increases Mitochondrial Fusion and Bioenergetic

Fionnuala B. Hickey James B. Corcoran Brenda Walker Griffin Úna Bhreathnach Heather Mortiboys

Induced in high glucose-1 (IHG-1) is a conserved mitochondrial protein associated with diabetic nephropathy (DN) that amplifies profibrotic transforming growth factor (TGF)-b1 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-b ,l eading to renal proximal tubule dedifferentiation, an important event in the pathogenesis of this devastating condition.

MFN1

MFN2

DNAJA3

Bioenergetics

Source

Cite

Citations (0)