Excessive mitochondrial fission in myocardial ischemia/reperfusion injury: Pathophysiological relevance and potential cardioprotective modulation by plant-derived interventions and electroacupuncture

Figure 1 Molecular machinery of mitochondrial fusion and fission. Mitochondrial fusion involves mitofusin 1 (MFN1) and MFN2, the long forms of optic atrophy 1 (L-OPA1) and short forms of optic atrophy 1 (S-OPA1), and cardiolipin (CL). MFN1 and MFN2 mediate outer mitochondrial membrane (OMM) tethering and fusion through trans interactions, oligomeric rearrangement, and guanosine triphosphate hydrolysis. At the inner mitochondrial membrane, membrane-anchored L-OPA1 interacts with CL on the opposing membrane to promote membrane tethering and fusion. S-OPA1 can cooperate with L-OPA1 in OPA1-dependent membrane remodeling, although the precise functional division between the two forms remains incompletely defined. Mitochondrial fission involves the endoplasmic reticulum (ER) or sarcoplasmic reticulum (SR), dynamin-related protein 1 (Drp1), and OMM-associated receptor or adaptor proteins, including mitochondrial fission factor, mitochondrial fission 1 protein, and mitochondrial dynamics proteins of 49 kDa and mitochondrial dynamics proteins of 51 kDa (MiD49 and MiD51). ER/SR-mitochondria contact sites mark and partially constrict prospective division sites. Drp1 is subsequently recruited from the cytosol to the OMM, where it assembles into oligomeric rings or helices. Guanosine triphosphate hydrolysis drives conformational changes in the Drp1 oligomer, promoting further membrane constriction and mitochondrial scission. MFN1/2: Mitofusin 1/2; L-OPA1: Long forms of optic atrophy 1; S-OPA1: Short forms of optic atrophy 1; CL: Cardiolipin; ER: Endoplasmic reticulum; SR: Sarcoplasmic reticulum; Drp1: Dynamin-related protein 1.