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

Authors
 Eunjin Koh  ;  Young Kyung Kim  ;  Daye Shin  ;  Kyung-Sup Kim 
Citation
 Biochemical Journal, Vol.475(10) : 1687-1699, 2018 
Journal Title
 Biochemical Journal 
ISSN
 0264-6021 
Issue Date
2018
Keywords
PGC-1alpha ; mitochondrial pyruvate carrier ; renal cell carcinoma
Abstract
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.
DOI
10.1042/BCJ20170967
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실)
Yonsei Authors
고은진(Koh, Eun Jin) ORCID logo https://orcid.org/0000-0001-8967-6266
김경섭(Kim, Kyung Sup) ORCID logo https://orcid.org/0000-0001-8483-8537
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/163464
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