24:T4d5,In contrast to long-term metabolic reprogramming, metabolic rewiring represents an instant and reversible cellular adaptation to physiological or pathological stress. Ca²⁺ signals of distinct spatio-temporal patterns control a plethora of signaling processes and can determine basal cellular metabolic setting, however, Ca²⁺ signals that define metabolic rewiring have not been conclusively identified and characterized. Here, we reveal the existence of a basal Ca²⁺ flux originating from extracellular space and delivered to mitochondria by Ca²⁺ leakage from inositol triphosphate receptors in mitochondria-associated membranes. This Ca²⁺ flux primes mitochondrial metabolism by maintaining glycolysis and keeping mitochondria energized for ATP production. We identified citrin, a well-defined Ca²⁺-binding component of malate-aspartate shuttle in the mitochondrial intermembrane space, as predominant target of this basal Ca²⁺ regulation. Our data emphasize that any manipulation of this ubiquitous Ca²⁺ system has the potency to initiate metabolic rewiring as an instant and reversible cellular adaptation to physiological or pathological stress.25:T412,Sigma-1 receptor (S1R) is an important endoplasmic reticulum chaperone with various functions in health and disease. The purpose of the current work was to elucidate the involvement of S1R in cancer energy metabolism under its basal, activated, and inactivated states. For this, two cancer cell lines that differentially express S1R were treated with S1R agonist, (+)-SKF10047, and antagonist, BD1047. The effects of the agonist and antagonist on cancer energy metabolism were studied using single-cell fluorescence microscopy analysis of real-time ion and metabolite fluxes. Our experiments revealed that S1R activation by agonist increases mitochondrial bioenergetics of cancer cells while decreasing their reliance on aerobic glycolysis. S1R antagonist did not have a major impact on mitochondrial bioenergetics of tested cell lines but increased aerobic glycolysis of S1R expressing cancer cell line. Our findings suggest that S1R plays an important role in cancer energy metabolism and that S1R ligands can serve as tools to modulate it.

#	Concept	H-Index	Publications	Citations
1	Medicine	1	1	25
2	Cell Biology	1	1	25
3	Immunology	1	1	25
4	Pathology	1	1	25
5	Cell Signaling	1	1	25

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