Although there has been considerable debate about whether paternal mitochondrial 
DNA (mtDNA) transmission may coexist with maternal transmission of mtDNA, it is 
generally believed that mitochondria and mtDNA are exclusively maternally 
inherited in humans. Here, we identified three unrelated multigeneration 
families with a high level of mtDNA heteroplasmy (ranging from 24 to 76%) in a 
total of 17 individuals. Heteroplasmy of mtDNA was independently examined by 
high-depth whole mtDNA sequencing analysis in our research laboratory and in two 
Clinical Laboratory Improvement Amendments and College of American 
Pathologists-accredited laboratories using multiple approaches. A comprehensive 
exploration of mtDNA segregation in these families shows biparental mtDNA 
transmission with an autosomal dominantlike inheritance mode. Our results 
suggest that, although the central dogma of maternal inheritance of mtDNA 
remains valid, there are some exceptional cases where paternal mtDNA could be 
passed to the offspring. Elucidating the molecular mechanism for this unusual 
mode of inheritance will provide new insights into how mtDNA is passed on from 
parent to offspring and may even lead to the development of new avenues for the 
therapeutic treatment for pathogenic mtDNA transmission.