Nuclear-mitochondrial genetic mismatch elicits an interferon-mediated cellular immune response

In this study, we used mRNA-Seq and functional assays to investigate the transcriptomic and cellular responses to nuclear-mitochondrial genetic mismatches using the xenomitochondrial cybrid panel. RNA-Seq revealed a remarkable reprogramming of nuclear gene expression in response to variation in the mitochondrial genome that involved adaptive changes in cellular metabolism and cell cycle regulation. Unexpectedly, we found that nuclear-mitochondrial mismatch elicits a strong interferon-mediated cellular response We have previously generated a panel of rodent xenomitochondrial cybrid cell lines that contain identical nuclear DNA (from the common laboratory strain Mus musculus domesticus) and mtDNA from progressively more divergent species relative to Mus musculus domesticus, including Mus spretus, Mus terricolor (formerly known as Mus dunni), Mus caroli, Mus pahari, Rattus norvegicus or Otomys irroratus, which represent mitochondrial genetic variance spanning 2-12 million years (McKenzie 2003; PMID: 12777531). In this work, we performed RNA-seq on these lines in triplicate.