Mitochondrial dynamics in heart disease

Abstract

Mitochondrial fission and fusion have been observed, and their importance revealed, in almost every tissue and cell type except adult cardiac myocytes. As each human heart is uniquely dependent upon mitochondria to generate massive amounts of ATP that fuel its approximately 38 million contractions per year, it seems odd that cardiac myocytes are the sole exception to the general rule that mitochondrial dynamism is important to function. Here, I briefly review the mechanisms for mitochondrial fusion and fission and examine current data that dispel the previous notion that mitochondrial fusion is dispensable in the heart. Rare and generally overlooked examples of cardiomyopathies linked either to naturally-occurring mutations or to experimentally-induced mutagenesis of mitochondrial fusion/fission genes are described. New findings from genetically targeted Drosophila and mouse models wherein mitochondrial fusion deficiency has specifically been induced in cardiac myocytes are discussed.

Pim-1 preserves mitochondrial morphology by inhibiting dynamin-related protein 1 translocation

“…Why mitochondria undergo fusion and fission is not well understood, but it is hypothesized that fission and fusion allow for complementation of mitochondrial mutations and elimination of dysfunctional mitochondria, thereby preserving functional mitochondrial populations (23). Mitochondrial fission and fusion classically involve the participation of five individual proteins: Drp1, Mfn1, Mfn2, Fis1, and Opa1.…”

Protein kinetic signatures of the remodeling heart following isoproterenol stimulation

“…Mitochondrial dynamics, in particular biogenesis, fusion-fission, and autophagy, play critical roles in cardiac functions (33)(34)(35). Our previous observations of diverse and asynchronous mitochondrial protein turnover in the normal mouse heart led us to conclude that the turnover of individual proteins can influence the homeostasis and dynamics of mitochondria (16,36).…”

Kruppel-like factor 4 is critical for transcriptional control of cardiac mitochondrial homeostasis

“…Since genes that regulate mitochondrial biogenesis and dynamics were altered in KLF4-deficient myocardium ( Figure 1E), we next sought to determine whether KLF4 also regulates mitochondrial biogenesis and dynamics in the heart. It has been reported that these processes are quite rare in the adult myocardium but critical for cardiac adaptation in the postnatal period (5,14,25). Thus, we chose to study perinatal cardiac development, as this period is notable for robust changes in mitochondrial biogenesis and dynamics.…”