Table 1.
Effect of mitochondrial morphology regulation on sensitivity to mitochondrial PT and apoptotic cell death
| Manipulation/Condition | Cell Type | Effect on Susceptibility to Permeability Transition and Apoptotic Cell Death | Reference |
|---|---|---|---|
| Pro-fusion (elongation) | |||
| DRP1 RNAi | HeLa | Delayed but does not inhibit apoptosis (STS, Act D) | 46 |
| DRP1 RNAi | HeLa | Reduced apoptosis (Eto) 40–50% at 24 h | 141 |
| DRP1K38A overexpression | COS-7 | Prevented release of cyt. c, decreased number of apoptotic cells with STS. | 48 |
| DRP1 shRNA | HeLa | Decreased apoptosis in response to pharmacological inducers (STS, Act D, α-Fas); less potent than DRP1 | 86 |
| DRP1K38A overexpression | HL-1 (cardiac) | Decreased cell death 60–80% 2 h after ischemia-reperfusion, decreased time to PT 50–60%* | 106 |
| DRP1K38A overexpression | H9c2 myoblasts | Prevented 1–7 fold induction of apoptosis (annexin V, caspase activation) during hyperglycemia | 162 |
| DRP1 inhibition (mdivi-1) | HL-1 (cardiac) | Decreased cell death 50–60% 40 mins after ischemia-reperfusion; prevented loss of membrane potential in permeabilized cardiomyocytes | 106 |
| αDRP1 antibody microinjection | HeLa | Decreased nuclear fragmentation 20 h after STS | 48 |
| Fis1 shRNA | HeLa | Decreased apoptosis in response to pharmacological inducers (STS, Act D, Eto, α-Fas) | 86 |
| MNF2 overexpression | Primary CGNs | Decreased cyt. c release and cell death after H2O2 treatment and DNA damage | 71 |
| MFN2 overexpression | HL-1 (cardiac) | Decreased cell death 50–70% 2 h after ischemia-reperfusion, decreased time to PT by 50–60%* | 106 |
| MFN1 overexpression | HL-1 (cardiac) | Decreased cell death 60–80% 2 h after ischemia-reperfusion, decreased time to PT by 50–60%* | 106 |
| OPA1 overexpression | Primary CGNs | Protected against cell death from excitotoxicity (Ca2+ stress) | 72 |
| Pro-fission (fragmentation) | |||
| OPA1 RNAi | HeLa | Increased sensitivity to apoptosis and increased spontaneous death | 86 |
| Fis1 overexpression | HL-1 (cardiac) | Increased cell death 40–60% 2 h after ischemia-reperfusion, no effect on time to PT | 106 |
| MFN1/2 RNAi | Hela | Increased apoptosis (Eto) 40–50% at 24 h | 141 |
| MFN2 KO | CGN (in vivo) | Neurodegeneration and increased abundance of TUNEL-positive CGN. | 28 |
| Mechanical isolation of mitochondria | Myofibers | Reduced time to Ca2+-induced PT opening by 98%, reduced calcium retention capacity by 50% | 115 |
PT, permeability transition; STS, sautosporine; Act D, actinomycin D; Eto, etoposide; α-Fas, anti-Fas receptor agonist; CGN, cerebellar granular neurons; DRP1K38A, dominant negative version of DRP1.
*
Effect similar in magnitude to that of cyclosporin A. MFN, mitofusin; OPA1, optic atrophy 1; shRNA, short hairpin RNA; RNAi, interfering RNA.