Is the mitochondrial cloud the selection machinery for preferentially transmitting wild-type mtDNA between generations? Rewinding Müller's ratchet efficiently.

In animal mitochondrial DNA inheritance, it remains largely unclear where the mitochondrial genetic bottleneck localizes and how it works in rewinding Müller's ratchet. In a variety of different animals germ plasm mRNAs typically aggregate along with numerous mitochondria to form the mitochondrial cloud (MC) during oogenesis. The MC has been found to serve as messenger transport organizer for germ plasm mRNAs. Germ plasm RNAs in MC will specifically distribute to the primordial germ cells of the future embryo. It has been proposed that the MC might be the site where selected mitochondria accumulate for specific transmission to grandchildren but this idea received relatively little attention and the criterion by which mitochondria are selected remains unknown. Our recent results in zebrafish provided further evidence for selective mitochondria accumulation in the MC by showing that mitochondria with high-inner membrane potential tend to be recruited preferentially into the MC, and these mitochondria are transported along with germ plasm to the cortex of the vegetal pole. By analyzing the composition, behavior and functions of the MC, and in reviewing related literature, we found strong support for the proposition that the MC corresponds to the position and function of the mitochondrial genetic bottleneck.