title: A novel defense system of mitochondria in mice and human subjects for preventing expression of mitochondrial dysfunction by pathogenic mutant mtDNAs.
abstract: Recently, we generated mtDNA-based disease mice (mito mice) by introduction of respiration-deficient mitochondria possessing pathogenic mutant mtDNA with a 4696 bp deletion (deltamtDNA4696) from somatic cells into mouse zygotes. Mito mice and cytochrome c oxidase (COX) electronmicrographs, that could identify the respiration enzyme activity at individual mitochondrial levels, enabled precise investigation of the pathogenesis of deltamtDNA4696. All the observations represented unambiguous evidence for the presence of extensive and continuous exchange of genetic contents between mitochondria. Thus, the inter-mitochondrial interaction could correspond to a very unique and effective defense system of the highly oxidative organelles for preventing mice and human subjects from expressing mitochondrial dysfunction caused by mtDNA lesions, which have been continuously created by oxidative stresses during aging. Here, we would like to propose a new hypothesis on mitochondrial biogenesis, 'the interaction theory of mammalian mitochondria': mitochondria exchange genetic contents, and thus lose individuality and function as a single dynamic cellular unit.
authors.affiliation: Institute of Biological Sciences, University of Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nakada
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ono
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Hayashi