Table 1.
Other Selected Functions of Core Mitochondrial Fusion and Fission Proteins
| Secondary function | Refs |
|---|---|
| DRP1 | |
| Peroxisome fission. | (354) |
| Binds to the ER and regulates ER morphology. | (314, 438) |
| Stimulates tBID-induced BAX oligomerization and cytochrome-c release by promoting tethering and hemifusion of membranes in vitro. | (269) |
| Localizes to the Golgi complex in some cell lines, potentially acting as a component of the apical sorting machinery at the trans-Golgi network. | (33) |
| During synaptic stimulation, BCL-XL translocates to clathrin-coated pits in a calmodulin-dependent manner and forms a complex with DRP1, MFF, and clathrin. | (217) |
| The DRP1-ABCD isoform is located at lysosomes and enriched at the inter-organelle interface between mitochondria and lysosomes/late endosomes. This enrichment depends on lysosomal pH. | (153) |
| FIS1 | |
| Peroxisomal adaptor for DRP1 | (183) |
| Interacts with BAP31 at the ER membrane to create a platform for activation of procaspase-8 during apoptosis. | (154) |
| MFF | |
| Peroxisomal adaptor for DRP1 | (114) |
| During synaptic stimulation, BCL-XL translocates to clathrin-coated pits in a calmodulin-dependent manner and forms a complex with DRP1, MFF, and clathrin. | (217) |
| MFN1 | |
| ER-MOM tethering. MFN2 on the ER engages heterotypic complexes with MFN1 on the surface of mitochondria. | (77) |
| MFN2 | |
| ER-MOM tethering. MFN2 on the ER engages in homotypic and heterotypic complexes with MFN1 or MFN2 on the surface of mitochondria. MFN2 knockdown increased Ca2+ transfer from the ER to mitochondria. | (14, 77, 203) |
| Suppresses vascular smooth muscle cell proliferation independent of its role in mitochondrial fusion. This growth suppression is inhibited by PKA-mediated phosphorylation of the Ser442 residue of MFN2. | (446) |
| Enhances mitochondrial metabolism. | (312) |
| MFN2 but not MFN1 is an ER stress-inducible protein that is required for the proper temporal sequence of the ER stress response. | (282) |
| MFN2 physically interacts with and is an upstream modulator of PERK, a protein involved in the response to ER stress stimuli by triggering the UPR. | (272) |
| In the heart, MFN2 serves as an adaptor protein to mediate fusion of autophagosomes and lysosomes. | (444) |
| Involved in trafficking of STIM1 to the ER-PM junction and subsequent activation of CRAC channel activity after Δψ depolarization. | (366) |
| Interacts with MIRO and MILTON to allow transport of axonal mitochondria. | (263) |
| MFN2 overexpression induces apoptosis in cardiac myocytes. | (361) |
| MFN2 exerts antiproliferative effects. | (55) |
| In BAT, MFN2 mediates the docking of mitochondria to LDs, allowing an efficient fatty acid transfer to mitochondria for β-oxidation. | (37) |
| MFN2 acts as a Parkin receptor on dysfunctional mitochondria. | (57) |
| MFN2 negatively regulates NFAT in the maintenance of HSCs with extensive lymphoid potential. In these cells, MFN2 increases ER-mitochondria tethering and therefore the cytosolic Ca2+-buffering capacity to inhibit NFAT activity. | (232) |
| MFN2 is important in maintaining coenzyme Q levels and might play a role in mevalonate synthesis. | (271) |
| OPA1 | |
| Organizes a supramolecular complex containing both PKA and Perilipin (PLIN1). OPA1 targeting of PKA to LDs is necessary for hormonal control of perilipin phosphorylation and lipolysis. | (313) |
BAP31, B cell receptor associated protein 31; BAT, brown adipose tissue; CRAC, calcium release-activated calcium channel; DRP1, dynamin-related protein 1; ER, endoplasmic reticulum; FIS1, fission protein 1; HSC, hematopoietic stem cell; LD, lipid droplet; MFF, mitochondrial fission factor; MFN1/MFN2, mitofusin 1 and 2; MIRO, mitochondrial RHO GTPase; MOM, mitochondrial outer membrane; NFAT, nuclear factor of activated T cells; OPA1, optic atrophy protein 1; PERK, protein kinase RNA (PKR)-like ER kinase; PKA, protein kinase A; PM, plasma membrane; STIM1, stromal interaction molecule 1; UPR, unfolded protein response.