Probing the pathogenicity of patient-derived variants of MT-ATP6 in yeast.

Autor:	Baranowska E; Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02106 Warsaw, Poland., Niedzwiecka K; Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02106 Warsaw, Poland., Panja C; Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02106 Warsaw, Poland., Charles C; University of Bordeaux, Centre National de la Recherche Scientifique, Institut de Biochimie et Génétique Cellulaires, UMR 5095, F-33000 Bordeaux, France., Dautant A; University of Bordeaux, Centre National de la Recherche Scientifique, Institut de Biochimie et Génétique Cellulaires, UMR 5095, F-33000 Bordeaux, France., Poznanski J; Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02106 Warsaw, Poland., di Rago JP; University of Bordeaux, Centre National de la Recherche Scientifique, Institut de Biochimie et Génétique Cellulaires, UMR 5095, F-33000 Bordeaux, France., Tribouillard-Tanvier D; University of Bordeaux, Centre National de la Recherche Scientifique, Institut de Biochimie et Génétique Cellulaires, UMR 5095, F-33000 Bordeaux, France., Kucharczyk R; Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02106 Warsaw, Poland.
Jazyk:	angličtina
Zdroj:	Disease models & mechanisms [Dis Model Mech] 2023 Apr 01; Vol. 16 (4). Date of Electronic Publication: 2023 Apr 21.
DOI:	10.1242/dmm.049783
Abstrakt:	The list of mitochondrial DNA (mtDNA) variants detected in individuals with neurodegenerative diseases is constantly growing. Evaluating their functional consequences and pathogenicity is not easy, especially when they are found in only a limited number of patients together with wild-type mtDNA (heteroplasmy). Owing to its amenability to mitochondrial genetic transformation and incapacity to stably maintain heteroplasmy, and the strong evolutionary conservation of the proteins encoded in mitochondria, Saccharomyces cerevisiae provides a convenient model to investigate the functional consequences of human mtDNA variants. We herein report the construction and energy-transducing properties of yeast models of eight MT-ATP6 gene variants identified in patients with various disorders: m.8843T>C, m.8950G>A, m.9016A>G, m.9025G>A, m.9029A>G, m.9058A>G, m.9139G>A and m.9160T>C. Significant defect in growth dependent on respiration and deficits in ATP production were observed in yeast models of m.8950G>A, m.9025G>A and m.9029A>G, providing evidence of pathogenicity for these variants. Yeast models of the five other variants showed very mild, if any, effect on mitochondrial function, suggesting that the variants do not have, at least alone, the potential to compromise human health. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2023. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu