Because mitochondrial diseases (diseases due to malfunction of mitochondria) can be inherited both maternally and through chromosomal inheritance, the way in which they are passed on from generation to generation can vary greatly depending on the disease. Mitochondrial genetic mutations that occur in the nuclear DNA can occur in any of the chromosomes (depending on the species). Mutations inherited through the chromosomes can be autosomal dominant or recessive and can also be sex-linked dominant or recessive. Chromosomal inheritance follows normal Mendelian laws, despite the fact that the phenotype of the disease may be masked. Because of the complex ways in which mitochondrial and nuclear DNA "communicate" and interact, even seemingly simple inheritance is hard to diagnose. A mutation in chromosomal DNA may change a protein that regulates (an increase or decrease) the production of another certain protein in the mitochondria or the cytoplasm and may lead to slight, if any, noticeable symptoms. On the other hand, there are some devastating mtDNA mutations that are easy to diagnose because of their widespread damage to muscular, neural, and/or hepatic (among other high energy and metabolism dependent) tissues and because they are present in the mother and all the offspring. Mitochondrial genome mutations are passed on 100% of the time from mother to all her offspring. Because the mitochondria within the fertilized oocyte is what the new life will have to begin with (in terms of mtDNA), and because the number of affected mitochondria varies from cell (in this case, the fertilized oocyte) to cell depending both on the number it inherited from its mother cell and environmental factors which may favor mutant or wildtype mitochondrial DNA, and because the number of mtDNA molecules in the mitochondria varies from around two to ten, the number of affected mtDNA molecules inherited to a specific offspring can vary greatly. It is possible, even in twin births, for one baby to receive more than half mutant mtDNA molecules while the other twin may receive only a tiny fraction of mutant mtDNA molecules with respect to wildtype (depending on how the twins divide from each other and how many mutant mitochondria happen to be on each side of the division). In a few cases, some mitochondria or a mitochondrion from the sperm cell enters the oocyte but paternal mitochondria are actively decomposed.
