Porter George A, Hom Jennifer, Hoffman David, Quintanilla Rodrigo, de Mesy Bentley Karen, Sheu Shey-Shing
Department of Pediatrics, University of Rochester Medical Center, 601 Elmwood Ave., Rochester, NY, USA.
Prog Pediatr Cardiol. 2011 May;31(2):75-81. doi: 10.1016/j.ppedcard.2011.02.002.
Cardiac metabolism is finely tuned, and disruption of myocardial bioenergetics can be clinically devastating. Many cardiomyopathies that present early in life are due to disruption of the maturation of these metabolic pathways. However, this bioenergetic maturation begins well before birth, when the embryonic heart is first beginning to beat, and continues into the mature animal. Thus, the changes in energy production seen after birth are actually part of a continuum that coincides with the structural and functional changes that occur as the cardiac myocyte differentiates and the heart undergoes morphogenesis. Therefore, although bioenergetics and mitochondrial biology have not been studied in great detail in the developing heart, bioenergetic maturation should be considered an important component of normal myocyte differentiation.Although events occurring after birth will be discussed, this review will focus on the changes in bioenergetics and mitochondrial biology that coincide with myocyte differentiation and cardiac morphogenesis. The relationship of these changes to the etiology and presentation of cardiomyopathies will be used as a starting point for this discussion. Then, after reviewing cardiac development and mitochondrial biology, the published data on bioenergetics and mitochondrial structure and function in the developing heart will be presented. Finally, the case will be made that mitochondria may be critical regulators of cardiac myocyte differentiation and cardiac development.
心脏代谢受到精细调节,心肌生物能量学的破坏在临床上可能具有毁灭性。许多在生命早期出现的心肌病是由于这些代谢途径成熟过程的破坏。然而,这种生物能量学成熟早在出生前就开始了,那时胚胎心脏刚开始跳动,并持续到成熟动物阶段。因此,出生后所见的能量产生变化实际上是一个连续过程的一部分,这与心肌细胞分化和心脏发生形态形成时出现的结构和功能变化相吻合。所以,尽管在发育中的心脏中生物能量学和线粒体生物学尚未得到详细研究,但生物能量学成熟应被视为正常心肌细胞分化的一个重要组成部分。虽然将讨论出生后发生的事件,但本综述将重点关注与心肌细胞分化和心脏形态形成相吻合的生物能量学和线粒体生物学变化。这些变化与心肌病病因和表现的关系将作为本次讨论的起点。然后,在回顾心脏发育和线粒体生物学之后,将呈现关于发育中心脏生物能量学以及线粒体结构和功能的已发表数据。最后,将论证线粒体可能是心肌细胞分化和心脏发育的关键调节因子。