Table 1.
Evidence in the alterations in mitochondrial dynamics following oxygen-glucose deprivation/reoxygenation: in vitro studies.
Study Model |
Injury Model |
OGD | Reoxygenation | Interpretation | Reference | ||||
---|---|---|---|---|---|---|---|---|---|
Changes in Mitochondrial Dynamics | Mitochondrial Function/Morphology | Cell Survival |
Changes in Mitochondrial Dynamics | Mitochondrial Function/Morphology | Cell Survival |
||||
Mouse optic nerves |
60 min OGD | ↓ Drp-1 in cytosolic fraction |
- | - | - | - | - | OGD-induced mitochondrial fission | [13] |
HT22 murine hippocampal neuronal culture | 45 min OGD/5 h reoxygenation | - | ↑ Mitochondrial fragmentation | No activation of apoptosis | ↑ s-OPA1 | ↑ Rapid and irreversible fragmentation |
↑ Caspase 3/7 activation | An increase in rapid mitochondrial fragmentation and cell death were observed following OGD and OGD/R | [25] |
Cortical and hippocampal neuronal culture from 18-day embryonic Sprague-Dawley rats | 1 h OGD/24 h reoxygenation | - | Translocation OPA1 mitochondria to cytosol ↑ s-OPA1 (proteolytic process) Breakdown of OPA1 oligomer in mitochondria ↑ Mitochondrial fission |
↑ Mitochondria fragmented and with granular appearance | ↑ Cytochrome c release | OGD in neuronal cells induced mitochondrial fragmentation and cell death via alterations in OPA1 | [33] | ||
Primary astrocytic cultures | 3 h hypoxia/10 h reoxygenation | ↓ pDRP1 (ser637) | ↓ mitochondrial area ↓ mitochondrial length ↓ VDAC ↑ LC3 II content ↓↓ ATP |
↓ Astrocytic extensions ↓ Superoxide production |
- | ↓ mitochondrial area ↓ mitochondrial length ↓ number of mitochondria ↓ VDAC ↑ LC3 II content ↓ ATP |
↓ Astrocytic extensions ↓ Superoxide production |
Both hypoxia and reoxygenation caused mitochondrial fragmentation in primary astrocytes via increased mitochondrial fission | [31] |
Primary cortical neuronal culture |
3 h OGD/0.5-24 h reoxygenation | ↓ Drp1, ↓ p-Drp1 (ser616) ↓ Mfn2 ⇿OPA1, Fis1 |
↓ normal mitochondria ↑ poorly labeled mitochondria ↑ swollen mitochondria |
↑ apoptotic or necrotic signs | ↓ Drp1, p-Drp1 (0.5–24 h of OGD/R) ↓ p-Drp1 (ser616) (3 h of OGD/R) ↑ Mfn1 (1–24 h of reoxygenation) ↓Mfn2 (0.5–24 h of OGD/R) |
↑ VDAC (3-24 h of OGD/R) ↑ Complex V protein (1-24 h of OGD/R) ↑ mtDNA (12-24 h of OGD/R) ↑ numbers of large, swollen mitochondria with rupture/loss of internal cristae |
↓ neuronal viability | OGD in neuronal cells induced mitochondrial fragmentation and cell death via the imbalance of mitochondrial fission and mitochondrial fusion | [32] |
ATP, adenosine triphosphate; Drp1, dynamin-related protein-1; mtDNA, mitochondrial DNA; OGD, oxygen-glucose deprivation; OGD/R: oxygen-glucose deprivation/reoxygenation; OPA-1, optic atrophy protein1; s-OPA1: short isoform optic atrophy protein1; VDAC, voltage-dependent anion-selective channel 1.