LAUSR

Inorganic polyphosphate (polyP) is a ubiquitous biological polymer that is well-conserved throughout the evolution and various species. Isoenergetic with ATP, polyP is composed of multiple subunits of orthophosphate, linked together by phosphoanhydride bonds. PolyP plays divergent roles in mammalian cells. In mitochondria, polyP is involved in the induction of the calcium-activated mitochondrial permeability transition pore (mPTP), as well as in the stimulation of the calcium-induced cell death. Paradoxically, cells with reduced amounts of mitochondrial polyP showed higher levels of cell death in response to increased ROS. Here we show that decreased amount of polyP also decreases cells resistance to rotenone and heat-shock induced cytotoxicity. We also demonstrate that the presence of polyP in mammalian cells prevents the aggregation of the C-subunit of ATP synthase. These findings are in agreement with the recently proposed role of polyP as a molecular chaperone, involved in cell stress response. We hypothesize that polyP plays a dual role in the mitochondria-related cell death pathway: during the initial stress it protects mitochondria by preventing protein aggregation, while excessive stress leads to the mitochondrial calcium overload and, eventually, to the polyP-mediated activation of mPTP.