Green tea epigallocatechin gallate binds to and inhibits respiratory complexes in swelling but not normal rat hepatic mitochondria
•Epigallocatechin gallate does not affect normal mitochondrial functions.•Epigallocatechin gallate inhibits respiratory complexes in swelling mitochondria.•Epigallocatechin gallate binds to respiratory complexes in swelling mitochondria.•Swelling mitochondria consume more epigallocatechin gallate th...
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Published in | Biochemical and biophysical research communications Vol. 443; no. 3; pp. 1097 - 1104 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
17.01.2014
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Subjects | |
Online Access | Get full text |
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Summary: | •Epigallocatechin gallate does not affect normal mitochondrial functions.•Epigallocatechin gallate inhibits respiratory complexes in swelling mitochondria.•Epigallocatechin gallate binds to respiratory complexes in swelling mitochondria.•Swelling mitochondria consume more epigallocatechin gallate than normal ones.
Epigallocatechin gallate (EGCG), the major flavonoid in green tea, is consumed via tea products and dietary supplements, and has been tested in clinical trials. However, EGCG can cause hepatotoxicity in humans and animals by unknown mechanisms. Here EGCG effects on rat liver mitochondria were examined. EGCG showed negligible effects on oxidative phosphorylation at 7.5–100μM in normal mitochondria. However, respiratory chain complexes (RCCs) were profoundly inhibited by EGCG in mitochondria undergoing Ca2+ overload-induced mitochondrial permeability transition (MPT). As RCCs are located in mitochondrial inner membranes (IM) and matrix, it was reasoned that EGCG could not readily pass through IM to affect RCCs in normal mitochondria but may do so when IM integrity is compromised. This speculation was substantiated in three ways. (1) Purified EGCG-bound proteins were barely detectable in normal mitochondria and contained no RCCs as determined by Western blotting, but swelling mitochondria contained about 1.5-fold more EGCG-bound proteins which included four RCC subunits together with cyclophilin D that locates in mitochondrial matrix. (2) Swelling mitochondria consumed more EGCG than normal ones. (3) The MPT blocker cyclosporine A diminished the above-mentioned difference. Among four subunits of RCC II, only SDHA and SDHB which locate in mitochondrial matrix, but not SDHC or SDHD which insert into the IM, were found to be EGCG targets. Interestingly, EGCG promoted Ca2+ overload-induced MPT only when moderate MPT already commenced. This study identified hepatic RCCs as targets for EGCG in swelling but not normal mitochondria, suggesting EGCG may trigger hepatotoxicity by worsening pre-existing mitochondria abnormalities. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0006-291X 1090-2104 |
DOI: | 10.1016/j.bbrc.2013.12.110 |