Mitochondrial functional complementation in mitochondrial DNA-based diseases

Mitochondria exist in networks that are continuously remodeled through fusion and fission. Why do individual mitochondria in living cells fuse and divide continuously? Protein machinery and molecular mechanism for the dynamic nature of mitochondria have been almost clarified. However, the biological significance of the mitochondrial fusion and fission events has been poorly understood, although there is a possibility that mitochondrial fusion and fission are concerned with quality controls of mitochondria. trans-mitochondrial cell and mouse models possessing heteroplasmic populations of mitochondrial DNA (mtDNA) haplotypes are quite efficient for answering this question, and one of the answers is “mitochondrial functional complementation” that is able to regulate respiratory function of individual mitochondria according to “one for all, all for one” principle. In this review, we summarize the observations about mitochondrial functional complementation in mammals and discuss its biological significance in pathogeneses of mtDNA-based diseases.