The shape of things to come: mitochondrial fusion and fission in the adult heart

Abstract

This editorial refers to ‘Down-regulation of OPA1 alters mouse mitochondrial morphology, PTP function, and cardiac adaptation to pressure overload’, by J. Piquereau et al ., pp. 408–417, this issue. Mitochondrial research is undergoing something of a renaissance with the discovery that mitochondria are no longer considered to be static, rod-shaped organelles whose only role within the cell is to generate ATP. In fact, mitochondria are highly mobile organelles, capable of changing their shape by undergoing ‘fusion’ (to form elongated, interconnected mitochondria) and ‘fission’ (to form fragmented, discrete mitochondria).1,2 Changes in mitochondrial morphology are regulated by the evolutionarily conserved mitochondrial fusion proteins, mitofusins 1 and 2 (Mfn1 and Mfn2) and optic atrophy-1 (OPA1), and the mitochondrial fission proteins, dynamin-related peptide 1 (Drp1), mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (Mff), and mitochondrial dynamics proteins of 49 and 51 kDa (MiD49/51).1,2 Until recently, the investigation of mitochondrial dynamics and morphology had been largely confined to non-cardiovascular cells. However, a number of recent experimental studies have suggested that changes in mitochondrial morphology may play a role in the cardiovascular system in the settings of vascular smooth cell proliferation, cardiac development and differentiation, stem cell differentiation, myocardial ischaemia–reperfusion injury (IRI), and heart failure (reviewed in 1 and 2). Although the unique arrangement of mitochondria within the adult cardiomyocyte may limit their ability to move within the cell, the fact that the mitochondrial fusion and fission machinery is highly expressed in the adult myocardium would suggest that the mitochondrial fusion and fission proteins may have an important role to play in the adult heart. Whether mitochondrial dynamics are relevant to the post-mitotic adult heart is the subject of on-going investigation in several research laboratories, with recently published experimental studies implicating a role for the mitochondrial fission …