PT  - JOURNAL ARTICLE
AU  - Maria E Solesio
AU  - Luis C Garcia del Molino
AU  - Pia A Elustondo
AU  - Catherine Diao
AU  - Joshua C Chang
AU  - Evgeny V Pavlov
TI  - Inorganic polyphosphate (polyP) is required for sustained free mitochondrial calcium elevation, following stimulated calcium uptake
AID  - 10.1101/493825
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 493825
4099  - http://biorxiv.org/content/early/2018/12/13/493825.short
4100  - http://biorxiv.org/content/early/2018/12/13/493825.full
AB  - Mitochondrial free calcium is critically linked to the regulation of bioenergetics and cellular signaling. Free calcium concentrations within the organelle are regulated by two processes: flux across the mitochondrial inner membranes and buffering by phosphate. The key role of phosphate in the buffering of free calcium in mitochondria is well-established. Specifically, during stimulated calcium uptake, calcium is partially buffered by orthophosphate, allowing for elevated calcium concentrations, while preventing calcium toxicity. However, this buffering system is expected to lead to the irreversible formation of insoluble precipitates, which are not observed in living cells, under physiological conditions. Here, we demonstrate that the regulation of free mitochondrial calcium requires the presence of free inorganic polyphosphate (polyP) within the organelle. Specifically, we found that the overexpression of a mitochondrial-targeted enzyme hydrolyzing polyP, leads to the loss of the cellular ability to maintain elevated calcium concentrations within the organelle, following stimulated cytoplasmic signal. We hypothesize that the presence of polyP prevents the formation of calcium-phosphate insoluble clusters, allowing for the maintenance of elevated free calcium levels, during stimulated calcium uptake.