IGF-1 boosts mitochondrial function by a Ca2+ uptake-dependent mechanism in cultured human and rat cardiomyocytes
| Autor: | Sánchez-Aguilera, Pablo, López-Crisosto, Camila, Norambuena-Soto, Ignacio, Penannen, Christian, Zhu, Jumo, Bomer, Nils, Hoes, Matijn F., Van Der Meer, Peter, Chiong, Mario, Westenbrink, B. Daan, Lavandero, Sergio |
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| Přispěvatelé: | Genetica & Celbiologie, RS: Carim - H02 Cardiomyopathy, Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Cardiovascular Centre (CVC) |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: |
STRESS
Physiology neonatal rat ventricular myocytes (NRVMs) CCDC90A METABOLISM CALCIUM UNIPORTER DISEASE physiological cardiac hypertrophy ACTIVATION Physiology (medical) insulin-like growth factor 1 (IGF-1) mitochondrial calcium handling MCU complex human embryonic stem cell derived-cardiomyocytes (hES-CMs) HEART-FAILURE REGULATOR MCUR1 |
| Zdroj: | Frontiers in physiology, 14:1106662. Frontiers Media S.A. Frontiers in Physiology, 14:1106662. Frontiers Media SA |
| ISSN: | 1664-042X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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