Sympatric Drosophila simulans flies with distinct mtDNA show age related differences in mitochondrial metabolism

Abstract

The primary causes of age related changes in mitochondrial metabolism are not known. The goal of this study is to document the influence of naturally occurring mtDNA variation on age dependent changes in mitochondrial respiration, hydrogen peroxide (H 2 O 2 ) generation and antioxidant defenses in the fly Drosophila simulans. Possible changes include an increase in rates of reactive oxygen species production with age and/or an age dependent decrease in antioxidant response. For this study we have used flies harboring distinct siII and siIII mtDNA types. Previously we have shown that males harboring siII mtDNA had higher rates 30 of mitochondrial H 2 O 2 production from complex III at 11 d compared to males with the siIII mtDNA type. Here, we corroborate those results and show that Drosophila harboring the siII and siIII mtDNA types exhibit significantly different patterns of pro-oxidant and antioxidant activities as they age. Flies harboring siII mtDNA had higher rates of mitochondrial H 2 O 2 production and manganese superoxide dismutase activity at 11 and 18 d of age than siIII mtDNA 35 harboring flies. Copper-zinc superoxide dismutase activity increased from 11 to 25 d in siII flies while the accumulation of oxidized glutathione did not change between 11 and 25 d. In contrast, siIII harboring flies showed an age dependent increase in H 2 O 2 production, reaching higher production rates on day 25 than that observed in siII flies. Copper-zinc superoxide dismutase activities did not change between 11 and 25 d while the oxidized glutathione accumulation increased with age. The results show antioxidant levels correlate with pro-oxidant levels in siII but not siIII flies. These results demonstrate our ability to correlate mtDNA variation with differences in whole mitochondrial physiology and individual complex biochemistry.

Sex-specific effects of sympatric mitonuclear variation on fitness in Drosophila subobscura

“…Our study adds to a handful of studies demonstrating important functional phenotypic differences between sympatric mtDNA haplotypes, in vivo [ 13 , 26 – 28 , 39 ] as well as in vitro [ 40 – 42 ]. Collectively, this empirical body of research suggests that the long-standing view of segregating mtDNA variation as being selectively neutral may often be misplaced.…”

Sex differences in survival and mitochondrial bioenergetics during aging inDrosophila

“…In the longer‐lived genetic crosses, MnSOD and Cu/ZnSOD levels tended to be higher in females suggesting that bolstering SOD defenses may only be effective in compromised genetic backgrounds (Orr & Sohal, 2003). In contrast to these results, Katewa & Ballard 2007) compared ROS production in two groups of male D. simulans flies harboring distinct mtDNA haplogroups and found that ROS production differed in the two haplogroups but only one group showed an age‐dependent increase. Furthermore, several studies have failed to find any difference in rates of H 2 O 2 production in Drosophila , either with age (Miwa et al ., 2004), or between long‐lived diet‐restricted flies (Magwere et al ., 2006a), or in flies exhibiting high levels of activity (Magwere et al ., 2006b).…”

Within‐population genetic effects of mtDNA on metabolic rate in Drosophila subobscura

“…However, very few studies have explored phenotypic effects of sympatrically occurring mtDNA variants, which is unfortunate given that natural selection primarily acts within populations. In Drosophila simulans , sympatric mtDNA haplotypes do show differences in in vitro assays of metabolic function (Katewa & Ballard, ; Pichaud et al ., ). Similarly, Dowling et al .…”