Abstract
Mitochondria are dynamic in nature and are able to shift their morphology between elongated interconnected mitochondrial networks and a fragmented disconnected arrangement by the processes of mitochondrial fusion and fission, respectively. Changes in mitochondrial morphology are regulated by the mitochondrial fusion proteins – mitofusins 1 and 2 (Mfn1 and 2), and optic atrophy 1 (Opa1) as well as the mitochondrial fission proteins – dynamin-related peptide 1 (Drp1) and fission protein 1 (Fis1). Despite having a unique spatial arrangement, cardiac mitochondria have been implicated in a variety of disorders including ischemia–reperfusion injury (IRI), heart failure, diabetes, and pulmonary hypertension. In this chapter, we review the influence of mitochondrial dynamics in these cardiac disorders as well as their potential as therapeutic targets in tackling cardiovascular disease.
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Abbreviations
- Akt:
-
Protein kinase B (PKB)
- ANT:
-
Adenine nucleotide translocator
- APOO:
-
Apolipoprotein O
- ATP:
-
Adenosine triphosphate
- Ca2+ :
-
Calcium ions
- CsA:
-
Cyclosporine A
- Cx-43:
-
Connexin-43
- CypD:
-
Cyclophilin D
- Drp1:
-
Dynamin-related peptide 1
- ER:
-
Endoplasmic reticulum
- ETC:
-
Electron transport chain
- FATP1:
-
Fatty acid transport protein 1
- Grp75:
-
Glucose-regulated protein 75
- GTPases:
-
Guanosine triphosphatases
- HKII:
-
Hexokinase II
- H2O2 :
-
Hydrogen peroxide
- IF:
-
Interfibrillar
- IMM:
-
Inner mitochondrial membrane
- IP3R:
-
Inositol 1,4,5-triphosphate receptor
- IR:
-
Ischemia–reperfusion
- IRI:
-
Ischemia–reperfusion injury
- KCl:
-
Potassium chloride
- LV:
-
Left ventricle
- MARF:
-
Mitochondrial assembly regulatory factor
- Mdivi-1:
-
Mitochondrial division inhibitor 1
- Mff:
-
Mitochondrial fission factor
- Mfn1:
-
Mitofusin 1
- Mfn2:
-
Mitofusin 2
- MI:
-
Myocardial infarct
- MiD49/51:
-
Mitochondrial dynamics proteins of 49 and 51 kDa
- MLKL:
-
Mixed lineage kinase domain like protein
- MMP:
-
Mitochondrial membrane potential
- MOMP:
-
Mitochondrial outer membrane permeabilization
- mPTP:
-
Mitochondrial permeability transition pore
- mTOR:
-
Mechanistic target of rapamycin
- OMM:
-
Outer mitochondrial membrane
- Opa1:
-
Optic atrophy 1
- OPA1-KD:
-
OPA1-knockdown
- PAH:
-
Pulmonary arterial hypertension
- pAkt:
-
Phospho-Akt
- PASMC:
-
Pulmonary artery smooth muscle cell
- PERK:
-
Protein kinase RNA-like endoplasmic reticulum kinase
- PGC-1α:
-
PPAR gamma coactivator-1
- PiC:
-
Inorganic phosphate carrier
- PPAR:
-
Peroxisome proliferator-activated receptor
- RIP:
-
Receptor-interacting protein
- ROS:
-
Reactive oxygen species
- SENP3:
-
SUMO1/sentrin/SMT3 specific peptidase 3
- sI:
-
Simulated ischemia
- sIRI:
-
Simulated ischemia–reperfusion injury
- siRNA:
-
Small interfering RNA
- Smac/DIABLO:
-
Second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI
- SSC:
-
Subsarcolemmal
- SUMOs:
-
Small ubiquitin-like modifiers
- TNF-α:
-
Tumor necrosis factor alpha
- UPR:
-
Unfolded protein response
- VDAC:
-
Voltage-dependent anion channel
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Acknowledgements
Sang-Bing Ong is supported by the Singapore Ministry of Health’s National Medical Research Council under its Open Fund—Young Individual Research Grant (OF-YIRG) scheme and a Khoo Postdoctoral Fellowship Award (KPFA) from the Estate of Tan Sri Khoo Teck Puat, Singapore. Derek John Hausenloy was supported by the British Heart Foundation (FS/10/039/28270), the Rosetrees Trust, and the National Institute for Health Research University College London Hospitals Biomedical Research Centre.
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Ong, SB., Hausenloy, D.J. (2016). Mitochondrial Dynamics as a Therapeutic Target for Treating Cardiac Diseases. In: Singh, H., Sheu, SS. (eds) Pharmacology of Mitochondria. Handbook of Experimental Pharmacology, vol 240. Springer, Cham. https://doi.org/10.1007/164_2016_7
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