Fig. 7.

mito-Mendelian genetics and mitochondrial economy in penetrance and metabolism. A) Genetic mutations exist in both genomes (Mitochondrial and Nuclear) that irrespective of their genomic combination, will be highly penetrant and therefore exhibit either Mendelian or mitochondrial genetic transmission (indicated by blue and open arrows, respectively). By contrast, we predict that many common metabolic diseases will follow a mito-Mendelian form (indicated by bracket) of inheritance in which penetrance will be modulated by mitochondrial metabolism that is guided by mtDNA – nDNA background combination (in response to stress factors). B) After the energetic requirements of the cell are met, mtDNA-nDNA combinations that are linked with low (more utilization of electrons for ATP generation) or high (less utilization of electrons for ATP generation) levels of mitochondrial economy will be also linked to lower or higher levels of oxidant production, CAC intermediates, and mitochondrial (Mt) DAMPs with stress (e.g. positive energy balance), respectively.