Mitochondrial DNA maintenance in Drosophila melanogaster

Abstract

All 37 mitochondrial DNA (mtDNA)-encoded genes involved with oxidative phosphorylation and intramitochondrial protein synthesis, and several nuclear-encoded genes involved with mtDNA replication, transcription, repair and recombination are conserved between the fruit fly Drosophilamelanogaster and mammals. This, in addition to its easy genetic tractability, has made Drosophila a useful model for our understanding of animal mtDNA maintenance and human mtDNA diseases. However, there are key differences between the Drosophila and mammalian systems that feature the diversity of mtDNA maintenance processes inside animal cells. Here, we review what is known about mtDNA maintenance in Drosophila, highlighting areas for which more research is warranted and providing a perspective preliminary in silico and in vivo analyses of the tissue specificity of mtDNA maintenance processes in this model organism. Our results suggest new roles (or the lack thereof) for well-known maintenance proteins, such as the helicase Twinkle and the accessory subunit of DNA polymerase γ, and for other Drosophila gene products that may even aid in shedding light on mtDNA maintenance in other animals. We hope to provide the reader some interesting paths that can be taken to help our community show how Drosophila may impact future mtDNA maintenance research.

WITHDRAWN: Mitochondrial genome variation affects humoral and cell-mediated innate immune responses and infection outcomes

“…cybrid lines, where we introgressed specific mtDNA variants (mitotypes) into an isogenic nDNA background [6]. The content and function of the mtDNA is highly conserved between D. melanogaster and humans [6–8], making it possible to model various aspects of mtDNA variation. Previous studies used Drosophila cybrid lines to examine the effect of mtDNA variation, e.g.…”

Challenges and opportunities to bridge translational to clinical research for personalized mitochondrial medicine

“…Worth highlighting are the key contributions of three powerful genetic models, Drosophila melanogaster , Caenorhabditis elegans and Danio rerio (zebrafish) in mitochondrial biology, pathogenic mechanisms of PMDs, and the drug development process [ 66 , [78] , [79] , [80] ]. Although these animal models do not faithfully mimic the clinical symptoms associated with a specific PMD, they are easily amenable to genetic manipulations, which further our understanding of mitochondrial inheritance [ 81 , 82 ], discovery of novel disease alleles [ 83 , 84 ] and the molecular pathogenetic mechanisms linked to specific clinical symptoms in patients [ [85] , [86] , [87] ].…”

Boosting life sciences research in Brazil: building a case for a local Drosophila stock center

“…Importantly, 75-85% of genes associated with human diseases have an orthologue in Drosophila , and although the evolutionary lines that gave rise to insects and mammals split 500-600 million years ago, most genes retain a remarkable similarity and have conserved functions ( Ugur et al, 2016 ; Baldridge et al, 2021 ; Cook and Parks, 2022 ). Several human diseases have been modeled in Drosophila , including autism spectrum disorder ( Bellosta and Soldano, 2019 ), Alzheimer’s ( Tsuda and Lim, 2018 ; Tue et al, 2020 ), Parkinson’s ( Aryal and Lee, 2019 ), amyotrophic lateral sclerosis ( Goodman and Bonini, 2020 ; Liguori et al, 2021 ), cancer ( Chatterjee and Deng, 2019 ), diabetes ( Chatterjee and Perrimon, 2021 ), obesity ( Musselman and Kühnlein, 2018 ; Chatterjee and Perrimon, 2021 ), mitochondrial disorders ( Chen et al, 2019 ; Rodrigues et al, 2022 ) and muscular dystrophies ( Potikanond et al, 2018 ), among others. Therefore, investigating human biological processes/diseases and their associated genes in flies is not only possible, but also extremely informative.…”