Mutations of the mitochondrial ND1 gene as a cause of MELAS

omplex I is the largest of the mitochondrial respiratory chain enzyme complexes, consisting of at least 46 subunits, seven of which are encoded by mtDNA. Deficiency of complex I is the most common respiratory chain defect, and can be caused by mutations in both nuclear and mtDNA encoded genes. 2] Other mutations in MTTL1 and other transfer RNA genes (MTTF, MTTV, MTTQ) account for most of the remainder of cases. However, a number of mutations in the mitochondrial MTND subunit genes of complex I have also been reported to cause MELAS, most notably in MTND5 5 and to a lesser extent in MTND6. n stark contrast, there are presently no mutations in the MTND1 subunit gene associated with MELAS. 8] Evidence confirming the pathogenic nature of these mutations includes data from cell fusion experiments and blue native polyacrylamide gel electrophoresis (BN-PAGE), the latter confirming a crucial role for the ND1 subunit in the assembly of complex I holoenzyme.