Mitochondrial DNA variants influence mitochondrial bioenergetics in Drosophila melanogaster

Correa, Carolina; Aw, Wen C.; Melvin, Richard G; Pichaud, Nicolas; Ballard, J. William O.

doi:10.1016/j.mito.2012.06.005

Cited by 49 publications

(51 citation statements)

References 36 publications

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“…Variations in mitochondrial respiration on permeabilized muscle fibers were directly linked to naturally occurring mtDNA haplotypes, even in young flies. As flies aged, an increase in ROS production and copy number of mtDNA were observed in all strains and the percentage increase in each strain could be associated with the mtDNA haplotype and with longevity [22]. These experiments comply with the ruling hypothesis.…”

Section: Mitochondrial Dysfunction and Oxidative Stress In Aged Musupporting

confidence: 56%

Mitochondria in the Aging Muscles of Flies and Mice: New Perspectives for Old Characters

Campo

Jaimovich

Tevy

2016

Oxidative Medicine and Cellular Longevity

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Sarcopenia is the loss of muscle mass accompanied by a decrease in muscle strength and resistance and is the main cause of disability among the elderly. Muscle loss begins long before there is any clear physical impact in the senior adult. Despite all this, the molecular mechanisms underlying muscle aging are far from being understood. Recent studies have identified that not only mitochondrial metabolic dysfunction but also mitochondrial dynamics and mitochondrial calcium uptake could be involved in the degeneration of skeletal muscle mass. Mitochondrial homeostasis influences muscle quality which, in turn, could play a triggering role in signaling of systemic aging. Thus, it has become apparent that mitochondrial status in muscle cells could be a driver of whole body physiology and organismal aging. In the present review, we discuss the existing evidence for the mitochondria related mechanisms underlying the appearance of muscle aging and sarcopenia in flies and mice.

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Section: Mitochondrial Dysfunction and Oxidative Stress In Aged Musupporting

confidence: 56%

Mitochondria in the Aging Muscles of Flies and Mice: New Perspectives for Old Characters

Campo

Jaimovich

Tevy

2016

Oxidative Medicine and Cellular Longevity

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“…Further, this same fly line appeared to compensate for the mtDNA mutations and had the highest mtDNA copy number in 11 to 12‐ and 25 to 26‐day‐old males (Correa et al . ).…”

Section: Influence Of Mtdna‐encoded Mutationsmentioning

confidence: 97%

Mitochondrial DNA: more than an evolutionary bystander

2013

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Summary1. The vast majority of studies employing mtDNA in evolutionary biology and ecology have used it as a means to infer demographic and historical patterns without pondering the underlying functional implications. In contrast, the biochemical and medical communities often aim to understand the influence of specific mtDNA mutations on mitochondrial functions, but rarely consider the evolutionary and ecological implications. 2. Ongoing research has shown that mtDNA mutations can profoundly affect mitochondrial function in humans and other animals. If the mutation (or set of mutations) is pathogenic, mitochondrial malfunction may be detected from early age. In nature, however, most mutations are not highly deleterious and may exist at intermediate frequency in populations. 3. In this review, we suggest that knowledge of the underlying biochemistry and functions of mitochondria can facilitate a more complete determination of the evolutionary dynamics of mtDNA and its influence on the life-history traits of organisms. With this approach, it is possible to use biochemistry to link the genotype with the phenotype. 4. After reviewing the literature, we conclude that there can be physiological and evolutionary trade-offs in the way that mitochondrial mutations can affect age classes and/or fitness components and that these effects may depend on the environment. Through these trade-offs, it may be possible for specific mtDNA mutations to have unequal fitness in different nuclear genetic backgrounds and also in different environments.

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“…We saved the DNA fraction from all RNA extractions and purified the DNA by using the Gentra Puregene Tissue Kit (QIAGEN). We then measured mtDNA copy number per biological replicate, relative to a single-copy gene in the nuclear genome [31]. The parameter thus reflects the average number of mitochondrial DNA copies per cell (or nucleus).…”

Section: Gene-expression Quantificationmentioning

confidence: 99%

Single Nucleotides in the mtDNA Sequence Modify Mitochondrial Molecular Function and Are Associated with Sex-Specific Effects on Fertility and Aging

et al. 2015

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Mitochondria underpin energy conversion in eukaryotes. Their small genomes have been the subject of increasing attention, and there is evidence that mitochondrial genetic variation can affect evolutionary trajectories and shape the expression of life-history traits considered to be key human health indicators [1, 2]. However, it is not understood how genetic variation across a diminutive genome, which in most species harbors only about a dozen protein-coding genes, can exert broad-scale effects on the organismal phenotype [2, 3]. Such effects are particularly puzzling given that the mitochondrial genes involved are under strong evolutionary constraint and that mitochondrial gene expression is highly conserved across diverse taxa [4]. We used replicated genetic lines in the fruit fly, Drosophila melanogaster, each characterized by a distinct and naturally occurring mitochondrial haplotype placed alongside an isogenic nuclear background. We demonstrate that sequence variation within the mitochondrial DNA (mtDNA) affects both the copy number of mitochondrial genomes and patterns of gene expression across key mitochondrial protein-coding genes. In several cases, haplotype-mediated patterns of gene expression were gene-specific, even for genes from within the same transcriptional units. This invokes post-transcriptional processing of RNA in the regulation of mitochondrial genetic effects on organismal phenotypes. Notably, the haplotype-mediated effects on gene expression could be traced backward to the level of individual nucleotides and forward to sex-specific effects on fertility and longevity. Our study thus elucidates how small-scale sequence changes in the mitochondrial genome can achieve broad-scale regulation of health-related phenotypes and even contribute to sex-related differences in longevity.

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Mitochondrial DNA variants influence mitochondrial bioenergetics in Drosophila melanogaster

Cited by 49 publications

References 36 publications

Mitochondria in the Aging Muscles of Flies and Mice: New Perspectives for Old Characters

Mitochondria in the Aging Muscles of Flies and Mice: New Perspectives for Old Characters

Mitochondrial DNA: more than an evolutionary bystander

Single Nucleotides in the mtDNA Sequence Modify Mitochondrial Molecular Function and Are Associated with Sex-Specific Effects on Fertility and Aging

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