Disruption of the human COQ5-containing protein complex is associated with diminished coenzyme Q(10) levels under two different conditions of mitochondrial energy deficiency

作者：Yen Hsiu Chuan^*; Liu Yi Chun; Kan Chia Chi; Wei Hsing Ju; Lee Szu Hsien; Wei Yau Huei; Feng Yu Hsiu; Chen Chih Wei; Huang Chin Chang

来源：Biochimica et Biophysica Acta-General Subjects, 2016, 1860(9): 1864-1876.

DOI：10.1016/j.bbagen.2016.05.005

• High-molecular-weight protein complex
• Human COQ5
• Human COQ9
• Chemical uncoupler
• mtDNA mutation
• Secondary coenzyme Q(10) deficiency

Background: The Coq protein complex assembled from several Coq proteins is critical for coenzyme Q(6) (CoQ(6)) biosynthesis in yeast. Secondary CoQ(10) deficiency is associated with mitochondrial DNA (mtDNA) mutations in patients. We previously demonstrated that carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) suppressed CoQ(10) levels and COQ5 protein maturation in human 143B cells.
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 CoQ(10) 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 inhuman cells. Its destabilization was associated with reduced CoQ(10) levels and mitochondrial energy deficiency in human cells treated with FCCP or exhibiting MERRF mutation.
General significance: The findings elucidate a possible mechanism for mitochondrial dysfunction-induced CoQ(10) deficiency in human cells.

• 出版日期2016-9
• 单位长春大学