Journal
COMMUNICATIONS BIOLOGY
Volume 5, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s42003-022-03019-2
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Funding
- Austrian Science Fund (FWF) [DK-MCD W1226]
- MEFO Graz
- BioTechMed Graz
- Nikon Austria
- Medical University of Graz
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The study investigates the regulation of basal mitochondrial bioenergetics and reveals that Ca2+ fluxes from ER-mitochondria contact sites control basal mitochondrial metabolism and energetics. The researchers identify citrin as a primary regulator of this process and show that manipulation of Ca2+ dynamics can reprogram cellular and mitochondrial metabolism.
Koshenov et al. investigate the regulation of basal mitochondrial bioenergetics and find that Ca2+ fluxes from ER-mitochondria contact sites control basal mitochondrial metabolism and energetics. The authors identify citrin as a primary regulator of this process and show that manipulation of Ca2+ dynamics can reprogram cellular and mitochondrial metabolism. 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.
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