Mitochondrial dynamics and inter-mitochondrial communication in the heart.

Mitochondria are organelles highly dynamic in most types of cells, constantly changing morphology and forming dynamically continuous networks. Defects of mitochondrial dynamics are associated with various human diseases including neurodegenerative diseases and cardiovascular diseases. In the heart, mitochondria are rigidly organized between myofilaments into a crystal-like lattice pattern, the apparently limited mitochondrial movement raises the question of whether mitochondria communicate with each other dynamically. A large body of evidence reveals abnormal mitochondrial morphology in cardiac diseases and that deficiencies of mitochondrial dynamic related proteins lead to cardiac dysfunctions, indicating an essential role of mitochondrial dynamics in regulating the cardiac function. Here we will review mitochondrial dynamics in the heart with the focus on recent findings of the direct inter-mitochondrial communication in adult cardiomyocytes, and will discuss the possible regulating mechanisms.

C1q/tumor necrosis factor-related protein-3 enhances the contractility of cardiomyocyte by increasing calcium sensitivity.

C1q/tumor necrosis factor-related protein-3 (CTRP3) is an adipokine that protects against myocardial infarction-induced cardiac dysfunction through its pro-angiogenic, anti-apoptotic, and anti-fibrotic effects. However, whether CTRP3 can directly affect the systolic and diastolic function of cardiomyocytes remains unknown. Adult rat cardiomyocytes were isolated and loaded with Fura-2AM. The contraction and Ca2+ transient data was collected and analyzed by IonOptix system. 1 and 2µg/ml CTRP3 significantly increased the contraction of cardiomyocytes. However, CTRP3 did not alter the diastolic Ca2+ content, systolic Ca2+ content, Ca2+ transient amplitude, and L-type Ca2+ channel current. To reveal whether CTRP3 affects the Ca2+ sensitivity of cardiomyocytes, the typical phase-plane diagrams of sarcomere length vs. Fura-2 ratio was performed. We observed a left-ward shifting of the late relaxation trajectory after CTRP3 perfusion, as quantified by decreased Ca2+ content at 50% sarcomere relaxation, and increased mean gradient (µm/Fura-2 ratio) during 500-600ms (-0.163 vs. -0.279), 500-700ms (-0.159 vs. -0.248), and 500-800ms (-0.148 vs. -0.243). Consistently, the phosphorylation level of cardiac troponin I at Ser23/24 was reduced by CTRP3, which could be eliminated by preincubation of okadaic acid, a type 2A protein phosphatase inhibitor. In summary, CTRP3 increases the contraction of cardiomyocytes by increasing the myofilament Ca2+ sensitivity. CTRP3 might be a potential endogenous Ca2+ sensitizer that modulates the contractility of cardiomyocytes.