Mitochondria as Novel Players of the Cellular RNA Interference

Huang et al. (1) recently reported that mRNA-processing bodies, P-bodies, associate with mitochondria in human cells. Conversely, altering the mitochondrial permeability led to delocalization of Argonaute 2 (Ago2) from P-bodies and disrupted the formation of an active RNA-induced silencing complex (RISC). Meanwhile, we reported also in human cells the presence of Ago2 and a specific subset of microRNAs (2) at the mitochondria.

Remarkably, their mitochondrial localization correlated to earlier observations in rodents (3, 4). Besides, Ago2 was found associated with RNA transcribed from the mitochondrial genome (2, 5). Those studies are complementary in sketching mitochondria as novel players in the overall tuning of RNA interference (RNAi). The association of P-bodies and mitochondria (1) likely supports a dynamic molecular traffic between the two organelles. As raised by Huang et al. (1), the mitochondria may serve as a reservoir not only of microRNAs but also of ATP for RISC assembly in the P-bodies. On the other hand, our data (2) prompted us to hypothesize that Ago2 and microRNAs may be involved in regulating translation within mitochondria. Thereby mitochondria may be part of a more complex RNAi network within the cell. Altogether, those results raise the crucial issue of defining whether mitochondria are instrumental to RNAi or a target per se. Notwithstanding, the way is paved for a new field of research, which may unravel therapeutic outcomes to treat mitochondrial dysfunctions.