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.

Porcelli, A.M., Calvaruso, M.A., Iommarini, L., Kurelac, I., Zuntini, R., Ferrari, S., et al. (2016). A unique combination of rare mitochondrial ribosomal RNA variants affects the kinetics of complex I assembly. THE INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 75, 117-122 [10.1016/j.biocel.2016.04.007].

A unique combination of rare mitochondrial ribosomal RNA variants affects the kinetics of complex I assembly

PORCELLI, ANNA MARIA;IOMMARINI, LUISA;KURELAC, IVANA;ZUNTINI, ROBERTA;GASPARRE, GIUSEPPE
2016

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.
2016
Porcelli, A.M., Calvaruso, M.A., Iommarini, L., Kurelac, I., Zuntini, R., Ferrari, S., et al. (2016). A unique combination of rare mitochondrial ribosomal RNA variants affects the kinetics of complex I assembly. THE INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 75, 117-122 [10.1016/j.biocel.2016.04.007].
Porcelli, Anna Maria; Calvaruso, Maria Antonietta; Iommarini, Luisa; Kurelac, Ivana; Zuntini, Roberta; Ferrari, Simona; Gasparre, Giuseppe
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/537360
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