Prohibitin 2 Regulates Cell Proliferation and Mitochondrial Cristae Morphogenesis in Planarian Stem Cells

Prohibitins are pleiotropic proteins, whose multiple roles are emerging as key elements in the regulation of cell survival and proliferation. Indeed, prohibitins interact with several intracellular proteins strategically involved in the reg- ulation of cell cycle progression in response to extracellular growth signals. Prohibitins also have regulatory functions in mitochondrial fusion and cristae morphogenesis, phenomena related to the ability of self-renewing embryonic stem cells to undergo differentiation, during which mitochondria develop numerous cristae, increase in number, and generate an exten- sive reticular network. We recently identified a Prohibitin 2 homolog (DjPhb2) that is expressed in adult stem cells (neoblasts) of planarians, a well-known model system for in vivo studies on stem cells and tissue regeneration. Here, we show that in DjPhb2 silenced planarians, most proliferat- ing cells disappear, with the exception of a subpopulation of neoblasts localized along the dorsal body midline. Neoblast depletion impairs regeneration and, finally, leads animals to death. Our in vivo findings demonstrate that prohibitin 2 plays an important role in regulating stem cell biology, being involved in both the control of cell cycle progression and mitochondrial cristae morphogenesis.