Mitotype Interacts With Diet to Influence Longevity, Fitness, and Mitochondrial Functions in Adult Female Drosophila

Abstract

Mitochondrial DNA (mtDNA) and the dietary macronutrient ratio are known to influence a wide range of phenotypic traits including longevity, fitness and energy production. Commonly mtDNA mutations are posited to be selectively neutral or reduce fitness and, to date, no selectively advantageous mtDNA mutations have been experimentally demonstrated in adult female Drosophila. Here we propose that a ND V161L mutation interacted with diets differing in their macronutrient ratios to influence organismal physiology and mitochondrial traits, but further studies are required to definitively show no linked mtDNA mutations are functionally significant. We utilized two mtDNA types (mitotypes) fed either a 1:2 Protein: Carbohydrate (P:C) or 1:16 P:C diet. When fed the former diet, Dahomey females harboring the V161L mitotype lived longer than those with the Alstonville mitotype and had higher climbing, basal reactive oxygen species (ROS) and elevated glutathione S-transferase E1 expression. The short lived Alstonville females ate more, had higher walking speed and elevated mitochondrial functions as suggested by respiratory control ratio (RCR), mtDNA copy number and expression of mitochondrial transcription termination factor 3. In contrast, Dahomey females fed 1:16 P:C were shorter lived, had higher fecundity, walking speed and mitochondrial functions. They had reduced climbing. This result suggests that mtDNA cannot be assumed to be a strictly neutral evolutionary marker when the dietary macronutrient ratio of a species varies over time and space and supports the hypothesis that mtDNA diversity may reflect the amount of time since the last selective sweep rather than strictly demographic processes.

Mitonuclear conflict and cooperation govern the integration of genotypes, phenotypes and environments

“…This is true for both insects [26,53] and yeast [116]. Additional studies in Drosophila examining the influence of diet on mitochondrial effects reveal similar effects where factorial contrasts can be made [117,118]. An exception to this pattern comes from the w501 epistasis described above, where a strong mtDNA effect can dominate the proportion of variance explained in limited 2 mtDNAs × 2 nDNAs designs [111], but the mtDNA effect of w501 is diminished in larger mitonuclear genetic panels [105].…”

The Out of East Asia model versus the African Eve model of modern human origins in light of ancient mtDNA findings

“…Indeed, the 45000 year old Ust’-Ishim’s mtDNA had fewer SNPs to begin with and the one he did have are all common alleles in today’s population (>67%) except one site 16150 10 . The Asia model also regards mutations in mtDNA to be functional, which has ample evidential support 26,33,42,43 , and classifies haplotypes based on sharing of alleles with more weight on the slow evolving sites (altering protein or RNA sequences) 5 . Hence, the Asia model is inherently more sound and self-consistent than the Africa model due to stronger theoretical foundations and far more realistic assumptions.…”

Mitonuclear interactions produce extreme differences in response to redox stress

“…Given that many interventions also target complex I, even if downstream, we anticipate that other drug responses will be attenuated or amplified by mitonuclear interactions. Indeed, we and others have already shown substantial differences between mitonuclear genotypes in response to high-protein diets, so a systematic consideration of mitonuclear interactions in drug responses is overdue [47][48][49][50][51] .…”