Mitochondria contain their own DNA which is about 17,000 bp. Mutation in mtDNA can lead to a series of disorders known as mitochondrial disorders which will be very vivid in organs requiring high energy supply as brain, heart, eye & skeletal muscles. Owing to its oxidative function, mitochondria are having a high rate of mutations estimated to be 10 times that of nuclear DNA . However, mitochondrial disorders result also from mutations in nuclear DNA in the regions coding for mitochondrial components . For individuals having mitochondrial disorders resulting from mtDNA mutations , they have a mixture of mutated mtDNA & normal mtDNA which is a pattern of distribution known as mitochondrial DNA heteroplasmy. The proportion as well as the distribution of defective mtDNA influence the location , onset as well as severity of diseases.
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Conventional treatment of mitochondrial disorders is mainly supportive where patients are treated with co-enzyme Q10, which is a cofactor required for electron transfer from complexes I & II to complex III. However Gene Therapy & Modern Targetting Systems stepped in offering a radical & permenant cure for mitochondrial disorders. One of most promising strategies of Gene Therapy is allotropic expression which involves the engineering of normal genes then their introduction to nucleus. This method showed success in a mitochondrial disorder characterized by respiratory deficient phenotypes caused by a mutant MATP8 gene , where the engineered ATP gene has succeeded in production of ATPase 8 protein.
Modern targetting systems have developed offering a unique solution to mitochondrial disorders & overcoming the dilemma of heteroplasmy as well. Cell membarne Crossing Oligopolymers (CMCO’s) are molecules that are capable of penetrating cell membrane & selectively bind to mutated mtDNA inhibiting its replication. This technique has been successful in handling Oxidative Phosphorylation deficiency (OXPHOS deficiency).Tags: allotropic expression, CMCO's, heteroplasmy, mitochondria, mtDNA