Figure 9.

Schematic summarizing some of the pathways altered by the chronic loss of IP₃Rs and MCU. The acute responses to loss of ER–mitochondrial Ca²⁺ transport in cancer cells as documented in the literature (29, 30, 94) are shown above the dotted line. The adaptive chronic changes measured in the present study are shown below the dotted line. Upregulated or downregulated parameters are indicated by arrows colored red for IP₃R TKO and blue for MCU KO. The absence of an arrow indicates no change or minimal change in that parameter. Unlike acute effects, the chronic loss of ER–mitochondrial Ca²⁺ signaling maintains ATP levels and avoids bioenergetic failure. ER, endoplasmic reticulum; IP₃R, inositol trisphosphate receptor; MCU, mitochondrial Ca²⁺ uniporter.