scholarly journals Identification and Molecular Characterization of Peroxisome Proliferator-Activated Receptor δ as a Novel Target for Covalent Modification by 15-Deoxy-Δ12,14-prostaglandin J2

2018 ◽  
Vol 13 (12) ◽  
pp. 3269-3278 ◽  
Author(s):  
Aravind T. Reddy ◽  
Sowmya P. Lakshmi ◽  
Asoka Banno ◽  
Raju C. Reddy
Keyword(s):  
Molecular Characterization ◽  
Covalent Modification ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Novel Target ◽  
Prostaglandin J2

Molecular Characterization of Novel and Selective Peroxisome Proliferator-Activated Receptor α Agonists with Robust Hypolipidemic Activity in Vivo

2008 ◽  
Vol 75 (2) ◽  
pp. 296-306 ◽  
Author(s):  
Christopher D. Kane ◽  
Kimberly A. Stevens ◽  
James E. Fischer ◽  
Mehrdad Haghpassand ◽  
Lori J. Royer ◽  
...  
Keyword(s):  
Molecular Characterization ◽  
Hypolipidemic Activity ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

MPC1 is essential for PGC-1α-induced mitochondrial respiration and biogenesis

2018 ◽  
Vol 475 (10) ◽  
pp. 1687-1699 ◽  
Author(s):  
Eunjin Koh ◽  
Young Kyung Kim ◽  
Daye Shin ◽  
Kyung-Sup Kim
Keyword(s):  
Target Gene ◽  
Peroxisome Proliferator ◽  
Mitochondrial Matrix ◽  
Strong Suppression ◽  
Mitochondrial Oxygen Consumption ◽  
Peroxisome Proliferator Activated Receptor ◽  
Human Renal Cell Carcinoma ◽  
Mitochondrial Pyruvate Carrier ◽  
Novel Target ◽  
Estrogen Related Receptor

Mitochondrial pyruvate carrier (MPC), which is essential for mitochondrial pyruvate usage, mediates the transport of cytosolic pyruvate into mitochondria. Low MPC expression is associated with various cancers, and functionally associated with glycolytic metabolism and stemness. However, the mechanism by which MPC expression is regulated is largely unknown. In this study, we showed that MPC1 is down-regulated in human renal cell carcinoma (RCC) due to strong suppression of peroxisome proliferator-activated receptor-gamma co-activator (PGC)-1 alpha (PGC-1α). We also demonstrated that overexpression of PGC-1α stimulates MPC1 transcription, while depletion of PGC-1α by siRNA suppresses MPC expression. We found that PGC-1α interacts with estrogen-related receptor-alpha (ERR-α) and recruits it to the ERR-α response element motif located in the proximal MPC1 promoter, resulting in efficient activation of MPC1 expression. Furthermore, the MPC inhibitor, UK5099, blocked PGC-1α-induced pyruvate-dependent mitochondrial oxygen consumption. Taken together, our results suggest that MPC1 is a novel target gene of PGC-1α. In addition, low expression of PGC-1α in human RCC might contribute to the reduced expression of MPC, resulting in impaired mitochondrial respiratory capacity in RCC by limiting the transport of pyruvate into the mitochondrial matrix.

Sign in / Sign up

Export Citation Format

Share Document