The mitochondrial ADP/ATP carrier is a nuclear encoded protein, which catalyzes the exchange of ATP generated in mitochondria with ADP produced in the cytosol. In humans, mutations in the major ADP/ATP carrier gene, ANT1, are involved in several degenerative mitochondrial pathologies, leading to instability of mitochondrial DNA. Recessive mutations have been associated with mitochondrial myopathy and cardiomyopathy whereas dominant mutations have been associated with autosomal dominant Progressive External Ophtalmoplegia (adPEO). Recently, two de novo dominant mutations, R80H and R235G, leading to extremely severe symptoms, have been identified. In order to evaluate if the dominance is due to haploinsufficiency or to a gain of function, the two mutations have been introduced in the equivalent positions of the AAC2 gene, the yeast orthologue of human ANT1, and their dominant effect has been studied in heteroallelic strains, containing both one copy of wild type AAC2 and one copy of mutant aac2 allele. Through phenotypic characterization of these yeast models we showed that the OXPHOS phenotypes in the heteroallelic strains were more affected than in the hemiallelic strain indicating that the dominant trait of the two mutations is due to gain of function.

Dominance of yeast aac2R96H and aac2R252G mutations, equivalent to pathological mutations in ant1, is due to gain of function / Dallabona, Cristina; Baruffini, Enrico; Goffrini, Paola; Lodi, Tiziana. - In: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. - ISSN 0006-291X. - 493:2(2017), pp. 909-913. [10.1016/j.bbrc.2017.09.122]

Dominance of yeast aac2R96H and aac2R252G mutations, equivalent to pathological mutations in ant1, is due to gain of function

DALLABONA, Cristina;BARUFFINI, Enrico
Investigation
;
GOFFRINI, Paola
Investigation
;
LODI, Tiziana
2017

Abstract

The mitochondrial ADP/ATP carrier is a nuclear encoded protein, which catalyzes the exchange of ATP generated in mitochondria with ADP produced in the cytosol. In humans, mutations in the major ADP/ATP carrier gene, ANT1, are involved in several degenerative mitochondrial pathologies, leading to instability of mitochondrial DNA. Recessive mutations have been associated with mitochondrial myopathy and cardiomyopathy whereas dominant mutations have been associated with autosomal dominant Progressive External Ophtalmoplegia (adPEO). Recently, two de novo dominant mutations, R80H and R235G, leading to extremely severe symptoms, have been identified. In order to evaluate if the dominance is due to haploinsufficiency or to a gain of function, the two mutations have been introduced in the equivalent positions of the AAC2 gene, the yeast orthologue of human ANT1, and their dominant effect has been studied in heteroallelic strains, containing both one copy of wild type AAC2 and one copy of mutant aac2 allele. Through phenotypic characterization of these yeast models we showed that the OXPHOS phenotypes in the heteroallelic strains were more affected than in the hemiallelic strain indicating that the dominant trait of the two mutations is due to gain of function.
Dominance of yeast aac2R96H and aac2R252G mutations, equivalent to pathological mutations in ant1, is due to gain of function / Dallabona, Cristina; Baruffini, Enrico; Goffrini, Paola; Lodi, Tiziana. - In: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. - ISSN 0006-291X. - 493:2(2017), pp. 909-913. [10.1016/j.bbrc.2017.09.122]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2833236
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