Table 2.
Dynamic regulation of mitochondria
| Pathways | Key genes | Mechanisms | Roles | ||
|---|---|---|---|---|---|
| Mitochondrial fission | DRP1-mediated pathway | DRP1, Mff, Fis1, MiD49, MiD51 | The recruited DRP1 binds to the protein receptor (Mff, Fis1, MiD49 and MiD51), which breaks the inner and MOM, leading to mitochondrial fission. | Splitting of damaged mitochondria into two types of mitochondria with normal and abnormal function. | |
| Mitochondrial fusion | MFN1, MFN2 and OPA1-mediated pathways | MFN1, MFN2, OPA1 | The fusion of the MOM is mainly mediated by MFN1 and MFN2, while the fusion of the MIM is mediated by OPA1. | Maintains mitochondrial homeostasis by fusing damaged mitochondria with normal mitochondria to perform relatively normal functions. | |
| Mitophagy | PINK1/Parkin pathways | PINK1/Parkin | PINK1 aggregates at the MOM and recruits and activates Parkin, which in turn activates Parkin to polyubiquitinate a variety of mitochondrial protein substrates. Ultimately, mitophagy is induced by the action of LC3. | Mitophagy can wrap and remove damaged mitochondria from the cell through the autophagic pathway, thereby maintaining intracellular mitochondrial homeostasis. | |
| PINK1/Parkin-independent pathways | OPTN, NDP52, ULK1, DFCP1, WIPI1, synphilin-1 | PINK1 directly recruits OPTN and NDP52 to damaged mitochondria and subsequently recruits and activates ULK1, DFCP1 and WIPI1, which in turn induce mitophagy. PINK1-synphilin-1 complex induces mitophagy by recruiting SIAH-1 to accelerate the ubiquitination of proteins in damaged mitochondria. |
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| Receptor-mediated pathways | Receptors in the MOM | NIX/BNIP3L, BNIP3, FUNDC1, NLRX1, FKBP8, Bcl2L13 | The receptors located in the MOM all contain a binding site for the LC3 receptor, which can directly bind LC3 to induce mitophagy. | ||
| Receptors in the MIM | PHB2 and CL | Mitochondrial damage leads to the exposure of PHB2, which in turn binds to LC3; moreover, PHB2 induces mitophagy by stabilizing PINK1 and promoting PRKN/Parkin recruitment, protein ubiquitination and OPTN recruitment to mitochondria. CL transfer from MIM to MOM directly interacts with LC3 to induce mitophagy |
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DRP1: dynamin-related protein 1; Fis1: mitochondrial fission protein 1; Mff: mitochondrial fission factor; MFN1: mitochondrial fusion protein 1; MFN2: mitochondrial fusion protein 2; MiD49: mitochondrial dynamics protein 49; MiD51: mitochondrial dynamics protein 51; MIM: mitochondrial inner membrane; MOM: mitochondrial outer membrane; OPA1: optic atrophy 1 protein; OPTN: Optineurin; PINK1: PTEN-induced kinase 1; ULK1: unc-51 like kinase 1; WIPI1: WD repeat domain phosphoinositide interacting 1