A unique combination of rare mitochondrial ribosomal RNA variants affects the kinetics of complex I assembly. (June 2016)

• Record Type: Journal Article
• Authors: Porcelli, Anna Maria; Calvaruso, Maria Antonietta; Iommarini, Luisa; Kurelac, Ivana; Zuntini, Roberta; Ferrari, Simona; Gasparre, Giuseppe
• Is Part Of: International journal of biochemistry & cell biology. Volume 75(2016:Jun.)
• Page Start: 117
• Page End: 122
• Publication Date: 2016-06
• Subjects: mtDNA mitochondrial DNA -- rRNA ribosomal RNA -- CI respiratory complex I -- LHON Leber's Hereditary Optic Neuropathy -- MELAS Myoclonic Epilepsy with Lactic Acidosis and Stroke-like episodes -- 2D BN/SDS-PAGE two dimensional Blue Native sodium-dodecyl sulphate polyacrylamide gel electrophoresis -- HmtDB Human Mitochondrial DataBase -- 1D BN-PAGE first dimension Blue Native sodium-dodecyl sulphate polyacrylamide gel electrophoresis -- ROS reactive oxygen species; Mitochondrial rRNA mutations -- Bioenergetics -- Ribosomal structure -- Mitochondrial protein synthesis; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2016.04.007
• Languages: English
• ISSNs: 1357-2725

Abstract

Abstract: Mitochondrial DNA (mtDNA) mutations in respiratory complexes subunits contribute to a large spectrum of human diseases. Nonetheless, ribosomal RNA variants remain largely under-investigated from a functional point of view. We here report a unique combination of two rare mitochondrial rRNA variants detected by serendipity in a subject with chronic granulomatous disease and never reported to co-occur within the same mitochondrial haplotype. In silico prediction of the mitochondrial ribosomal structure showed a dramatic rearrangement of the rRNA secondary structure. Functional investigation of cybrids carrying this unique haplotype demonstrated that the co-occurrence of the two rRNA variants determines a slow-down of the mitochondrial protein synthesis, especially in cells with an elevated metabolic rate, which impairs the assembly kinetics of Complex I, induces a bioenergetic defect and stimulates reactive oxygen species production. In conclusion, our results point to a sub-pathogenic role for these two rare mitochondrial rRNA variants, when found in the unique combination here reported in a single individual.