Table 1.
Lessons from OMM proteins: mitochondrial fission does not essentially favor mitophagy.
| Protein | Action on mitochondrial dynamics | Role in mitophagy |
|---|---|---|
| Drp1 | A GTPase protein that accounts for mitochondrial fission. |
1. Facilitates PINK1/Parkin-dependent mitophagy [42, 109] and FUNDC1-mediated mitophagy [43]. 2. No effect on STX17-initiated mitophagy [39]. |
| Mff |
An OMM protein; A Drp1 receptor to support mitochondrial division. |
1. Facilitates PINK1/Parkin-dependent mitophagy [166]. 2. No effect on STX17-initiated mitophagy [39]. |
| Fis1 |
An OMM protein; A controversial role in fission–fusion. |
1. Promotes mitophagosome biogenesis for PINK1/Parkin-mediated mitophagy [133]. 2. Retards mitophagy by governing the over-assembly of STX17 on mitochondria. Loss of Fis1 primes cells for STX17-induced mitophagy [39]. |
| MiD49 |
An OMM protein; A Drp1 receptor to support mitochondrial division. |
Positively regulates PINK1/Parkin-dependent mitophagy. Loss of MiD49 decelerates PINK1/Parkin-dependent mitophagy [65]. |
| MiD51 |
An OMM protein; A Drp1 receptor to support mitochondrial division. |
Restrains PINK1/Parkin-dependent mitophagy. MiD51 loss accelerates Parkin translocation onto depolarized mitochondria [65] and mitophagy. |
| Mfn1 |
An OMM protein; GTPase activity required for mitochondrial fusion. |
1. Substrate of UPS induced by Parkin, which is preliminary for PINK1/Parkin-dependent mitophagy [109]; 2. Required for Gp78-dependent mitophagy upon mitochondrial depolarization [167]. |
| Mfn2 |
An OMM protein; GTPase activity required for mitochondrial fusion. |
1. Substrate of UPS induced by Parkin, which is preliminary for PINK1/Parkin-dependent mitophagy [109]; 2. At the early stage of mitochondrial depolarization, Mfn2 functions as an ER-mitochondria tether to prevent PINK1/Parkin-mediated mitophagy [118]; 3. At the late stage of PINK1/Parkin-mediated mitophagy, the UPS activation of Mfn2 is indispensable for mitophagy [65]. |
| OPA1 |
An IMM protein; GTPase activity required for mitochondrial fission or fusion (depending on disparate OPA1 isoforms). |
1. Negatively regulates basal mitophagy [168]; 2. A negative role to gate FUNDC1-mediated mitophagy [43]. |
OMM outer mitochondrial membrane, IMM inner mitochondrial membrane, UPS ubiquitin–proteasome system.