Table 2.
Effect of mitochondrial morphology regulation on mitochondrial respiratory properties
| Manipulation/Condition | Cell Type | Effect on Mitochondrial Respiration and ETC Function | Reference |
|---|---|---|---|
| Pro-fusion (elongation) | |||
| DRP1 RNAi | HeLa | Decreased respiration 60–70%, decreased ATP synthesis (abnormal budding of perinuclear mitochondria, experiments performed 96 h postinduction) | 10 |
| DRP1K38A overexpression | Clone 9 hepatocytes | Prevented a 40–50% increase in respiration during hyperglycemia | 162 |
| Mfn2 overexpression | H6E9 myotubes | Increased membrane potential and glucose oxidation rate (in the absence of network remodeling) | 117 |
| Pro-fission (fragmentation)* | |||
| Mfn1/Mfn2 double mutant | MEFs | Decreased respiration 30–70% under different energized states | 26 |
| Mfn2 antisense cDNA | 10T1/2 fibroblasts | Decreased respiration 20–40%, decreased membrane potential (in L6E9 myotubes) | 6 |
| Mfn2 mutations | Human fibroblasts | Decreased coupling efficiency 20–30% (ATP/O ratio) | 94 |
| Mfn2 mutations | Human fibroblasts | Decreased coupling efficiency 50–70% (ATP/O ratio), increased respiration with complex II-linked substrate | 24 |
| OPA1 mutation | Human fibroblasts | Decreased coupling efficiency 50% (ATP/O ratio) | 105 |
| OPA1 RNAi | MEFs | Decreased respiration 50–80% under different energized states | 26 |
| OPA1 mutations | Human fibroblasts | Decreased complex I-driven ATP synthesis | 166 |
| OPA1 KO | MEFs | Decreased ATP levels with starvation, impaired dimerization of ATP synthase | 54 |
MEF, mouse embryonic fibroblasts;
*
Loss of function of MFN2 and OPA1 has been linked to mitochondrial DNA instability (see text for details), which may impair respiratory chain function via mtDNA damage over periods exceeding several days, rather than via direct of mitochondrial morphology.