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

Autor: Porcelli AM; Dip. Farmacia e Biotecnologie (FABIT), Università di Bologna, via Irnerio 42, 40126 Bologna, Italy; Centro Interdipartimentale di Ricerca Industriale Scienze della Vita e Tecnologie per la Salute, Università di Bologna, 40100 Bologna, Italy., Calvaruso MA; Dip. Farmacia e Biotecnologie (FABIT), Università di Bologna, via Irnerio 42, 40126 Bologna, Italy., Iommarini L; Dip. Farmacia e Biotecnologie (FABIT), Università di Bologna, via Irnerio 42, 40126 Bologna, Italy., Kurelac I; Dip. Scienze Mediche e Chirurgiche (DIMEC), U.O. Genetica Medica, Pol. Universitario S. Orsola-Malpighi, Università di Bologna, via Massarenti 9, 40138 Bologna, Italy., Zuntini R; Dip. Scienze Mediche e Chirurgiche (DIMEC), U.O. Genetica Medica, Pol. Universitario S. Orsola-Malpighi, Università di Bologna, via Massarenti 9, 40138 Bologna, Italy., Ferrari S; Dip. Scienze Mediche e Chirurgiche (DIMEC), U.O. Genetica Medica, Pol. Universitario S. Orsola-Malpighi, Università di Bologna, via Massarenti 9, 40138 Bologna, Italy., Gasparre G; Dip. Scienze Mediche e Chirurgiche (DIMEC), U.O. Genetica Medica, Pol. Universitario S. Orsola-Malpighi, Università di Bologna, via Massarenti 9, 40138 Bologna, Italy. Electronic address: giuseppe.gasparre@gmail.com.
Jazyk: angličtina
Zdroj: The international journal of biochemistry & cell biology [Int J Biochem Cell Biol] 2016 Jun; Vol. 75, pp. 117-22. Date of Electronic Publication: 2016 Apr 19.
DOI: 10.1016/j.biocel.2016.04.007
Abstrakt: 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.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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