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G3 (Bethesda). 2019 Jul 9;9(7):2225-2234. doi: 10.1534/g3.119.400315.

Lethal Interaction of Nuclear and Mitochondrial Genotypes in Drosophila melanogaster.

Author information

1
Faculty of Medicine and Health Technology, FI-331014, University of Tampere, Finland.
2
Departamento de Tecnologia, Faculdade de Ciências Agrárias e Veterinárias, Universidade Estadual Paulista "Júlio de Mesquita Filho", Jaboticabal, SP 14884-900, Brazil.
3
Faculty of Medicine and Health Technology, FI-331014, University of Tampere, Finland howard.jacobs@tuni.fi lskaguni@msu.edu.
4
Institute of Biotechnology, FI-00014, University of Helsinki, Helsinki, Finland.
5
Department of Biochemistry and Molecular Biology and Center for Mitochondrial Science and Medicine, Michigan State University, East Lansing, MI 48824.

Abstract

Drosophila melanogaster, like most animal species, displays considerable genetic variation in both nuclear and mitochondrial DNA (mtDNA). Here we tested whether any of four natural mtDNA variants was able to modify the effect of the phenotypically mild, nuclear tko25t mutation, affecting mitochondrial protein synthesis. When combined with tko25t , the mtDNA from wild strain KSA2 produced pupal lethality, accompanied by the presence of melanotic nodules in L3 larvae. KSA2 mtDNA, which carries a substitution at a conserved residue of cytochrome b that is predicted to be involved in subunit interactions within respiratory complex III, conferred drastically decreased respiratory capacity and complex III activity in the tko25t but not a wild-type nuclear background. The complex III inhibitor antimycin A was able to phenocopy effects of the tko25t mutation in the KSA2 mtDNA background. This is the first report of a lethal, nuclear-mitochondrial interaction within a metazoan species, representing a paradigm for understanding genetic interactions between nuclear and mitochondrial genotype relevant to human health and disease.

KEYWORDS:

cybrid; cytochrome b; melanotic nodules; mtDNA copy number; respiration

PMID:
31076384
PMCID:
PMC6643882
DOI:
10.1534/g3.119.400315
[Indexed for MEDLINE]
Free PMC Article

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