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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Koshenov, Z; Oflaz, FE; Hirtl, M; Gottschalk, B; Rost, R; Malli, R; Graier, WF.
Citrin mediated metabolic rewiring in response to altered basal subcellular Ca2+ homeostasis.
Commun Biol. 2022; 5(1): 76
Doi: 10.1038/s42003-022-03019-2
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- Leading authors Med Uni Graz
- Graier Wolfgang
- Koshenov Zhanat
- Co-authors Med Uni Graz
- Gottschalk Benjamin
- Hirtl Martin
- Malli Roland
- Oflaz Furkan Enes
- Rost René
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- Abstract:
- 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.