Asymmetric segregation of mitochondria and mortalin correlates with the multi-lineage potential of inner ear sensory cell progenitors in vitro.

The sensory epithelia of the inner ear include hair cells and supporting cells that share a common precursor. One possible mechanism involved in the genesis of these cell types is through asymmetric cell division. In this work we have studied asymmetric division of inner ear sensory cell progenitors in vitro in an attempt to understand how the different cell phenotypes are generated. In the search for molecules that will segregate asymmetrically we have found that mitochondria in general, and a mitochondrial protein named mortalin in particular, are asymmetrically segregated during certain cell divisions. In one conditionally immortal cell line (UB/OC-1), which represents a population of committed hair cell precursors, mortalin is uniformly distributed in the cytoplasm and shared equally between sibling cells during division. In another cell line (UB/UE-1), which represents a bipotent, vestibular supporting cell that can produce both neonatal hair cells as well as supporting cells, mortalin segregates asymmetrically. In UB/UE-1, approximately 12% of the cells display an asymmetric distribution of mortalin and mitochondria. The proportion of asymmetric cells increases immediately after the release of the immortalizing gene and before the onset of differentiation. The asymmetric segregation of mortalin in the bipotent cell line and its uniform distribution in a committed, lineage-restricted cell line raises the possibility that it may play a role in cell fate determination.