Genotype to phenotype: Diet-by-mitochondrial DNA haplotype interactions drive metabolic flexibility and organismal fitness
The mitohormetic response, involving at least two separate pathways, enabled Dahomey to develop faster than Alstonville larvae. First, larvae with Dahomey mtDNA ate more, which caused third instar larvae to weigh more. Backup of sugars produced increased activity of the polyol pathway and increased N expression. Increased N expression blocked CrebB and fed back to increase food consumption. Second, pyruvate was metabolised to acetyl-CoA and exported from the mitochondrion for fatty acid synthesis and palmitic acid and stearic acid levels increased. The long-chain fatty acids were catabolised by β oxidation, resulting in the formation of NADH and FADH2. FADH2 shuttled electrons to the quinone pool and partially by-passed ETC complex I where the V161L mutation occurred. In contrast, Alstonville larvae upregulated glycogen metabolism and activity of the pentose phosphate pathway increased. Increased glycogen metabolism increased wandering, which diverted energy away from development. Increased insulin signalling decreased larval food consumption.