IGF-1 boosts mitochondrial function by a Ca2+ uptake-dependent mechanism in cultured human and rat cardiomyocytes
Open Access
- 8 February 2023
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Physiology
- Vol. 14, 1106662
- https://doi.org/10.3389/fphys.2023.1106662
Abstract
A physiological increase in cardiac workload results in adaptive cardiac remodeling, characterized by increased oxidative metabolism and improvements in cardiac performance. Insulin-like growth factor 1 (IGF-1) has been identified as a critical regulator of physiological cardiac growth, but its precise role in cardiometabolic adaptations to physiological stress remains unresolved. Mitochondrial calcium (Ca2+) handling has been proposed to be required for sustaining key mitochondrial dehydrogenase activity and energy production during increased workload conditions, thus ensuring the adaptive cardiac response. We hypothesized that IGF-1 enhances mitochondrial energy production through a Ca2+-dependent mechanism to ensure adaptive cardiomyocyte growth. We found that stimulation with IGF-1 resulted in increased mitochondrial Ca2+ uptake in neonatal rat ventricular myocytes and human embryonic stem cell-derived cardiomyocytes, estimated by fluorescence microscopy and indirectly by a reduction in the pyruvate dehydrogenase phosphorylation. We showed that IGF-1 modulated the expression of mitochondrial Ca2+ uniporter (MCU) complex subunits and increased the mitochondrial membrane potential; consistent with higher MCU-mediated Ca2+ transport. Finally, we showed that IGF-1 improved mitochondrial respiration through a mechanism dependent on MCU-mediated Ca2+ transport. In conclusion, IGF-1-induced mitochondrial Ca2+ uptake is required to boost oxidative metabolism during cardiomyocyte adaptive growth.Funding Information
- Agencia Nacional de Investigación y Desarrollo
This publication has 47 references indexed in Scilit:
- Mitochondrial fragmentation impairs insulin-dependent glucose uptake by modulating Akt activity through mitochondrial Ca2+ uptakeAmerican Journal of Physiology-Endocrinology and Metabolism, 2014
- The physiological role of mitochondrial calcium revealed by mice lacking the mitochondrial calcium uniporterNature, 2013
- Mitochondrial calcium uptakeProceedings of the National Academy of Sciences of the United States of America, 2013
- MCUR1 is an essential component of mitochondrial Ca2+ uptake that regulates cellular metabolismNature, 2012
- Fiji: an open-source platform for biological-image analysisNature Methods, 2012
- Role of Mitochondrial Ca2+ in the Regulation of Cellular EnergeticsBiochemistry, 2012
- Energy-preserving effects of IGF-1 antagonize starvation-induced cardiac autophagyCardiovascular Research, 2011
- Regulation of mitochondrial dehydrogenases by calcium ionsBiochimica et Biophysica Acta (BBA) - Bioenergetics, 2009
- Cardiac PlasticityThe New England Journal of Medicine, 2008
- Mitochondrial calcium transportFEBS Letters, 1980