Abstract | BACKGROUND: METHODS: This study explored the putative COQ protein complex in human cells through two-dimensional blue native- polyacrylamide gel electrophoresis and Western blotting to investigate its status in 143B cells after FCCP treatment and in cybrids harboring the mtDNA mutation that caused myoclonic epilepsy with ragged-red fibers ( MERRF) syndrome. Ubiquinol-10 and ubiquinone-10 levels were detected by high-performance liquid chromatography. Mitochondrial energy status, mRNA levels of various PDSS and COQ genes, and protein levels of COQ5 and COQ9 in cybrids were examined. RESULTS: A high-molecular-weight protein complex containing COQ5, but not COQ9, in the mitochondria was identified and its level was suppressed by FCCP and in cybrids with MERRF mutation. That was associated with decreased mitochondrial membrane potential and mitochondrial ATP production. Total CoQ10 levels were decreased under both conditions, but the ubiquinol-10: ubiquinone-10 ratio was increased in mutant cybrids. The expression of COQ5 was increased but COQ5 protein maturation was suppressed in the mutant cybrids. CONCLUSIONS: A novel COQ5-containing protein complex was discovered in human cells. Its destabilization was associated with reduced CoQ10 levels and mitochondrial energy deficiency in human cells treated with FCCP or exhibiting MERRF mutation. GENERAL SIGNIFICANCE:
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Authors | Hsiu-Chuan Yen, Yi-Chun Liu, Chia-Chi Kan, Hsing-Ju Wei, Szu-Hsien Lee, Yau-Huei Wei, Yu-Hsiu Feng, Chih-Wei Chen, Chin-Chang Huang |
Journal | Biochimica et biophysica acta
(Biochim Biophys Acta)
Vol. 1860
Issue 9
Pg. 1864-76
(09 2016)
ISSN: 0006-3002 [Print] Netherlands |
PMID | 27155576
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2016 Elsevier B.V. All rights reserved. |
Chemical References |
- DNA, Mitochondrial
- Mitochondrial Proteins
- RNA, Messenger
- Ubiquinone
- Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
- ubiquinol-10
- Methyltransferases
- COQ5 protein, human
- coenzyme Q10
- Ubiquinone Q2
- ubiquinone 9
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Topics |
- Ataxia
(genetics, metabolism)
- Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
(pharmacology)
- Cell Line
- DNA, Mitochondrial
(genetics)
- Humans
- MERRF Syndrome
(genetics, metabolism)
- Membrane Potential, Mitochondrial
(drug effects, genetics)
- Methyltransferases
(genetics, metabolism)
- Mitochondria
(drug effects, genetics, metabolism)
- Mitochondrial Diseases
(genetics, metabolism)
- Mitochondrial Proteins
(genetics, metabolism)
- Muscle Weakness
(genetics, metabolism)
- Mutation
(drug effects, genetics)
- RNA, Messenger
(genetics)
- Ubiquinone
(analogs & derivatives, deficiency, genetics, metabolism)
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