In addition to increased fission and decreased fusion rates, we found that BA mitochondria swelled after NE + FFA, showing a balloon shape with an enlargement of the matrix volume.
Although in Ku80 −/− MEFs the fusion frequency induced with TRF2 shRNA was reduced to approximately 64.7% relative to controls (Fig 3E and F), a much higher value than in TRF2-depleted Lig4 −/− MEFs (7.6%), CtIP inhibition in these cells further decreased fusion rates to 12.7%.
In a previous study, doxorubicin was shown to decrease spinal fusion rates in a rabbit model of lumbar intertransverse process spinal fusion with autograft iliac crest bone.
As a consequence, decreased mitochondrial fusion rates might be facilitating this mitochondrial swelling.
These results demonstrate that BA activation not only increased Drp1-mediated fission, but also decreased mitochondrial fusion rates.
Other studies have also shown that as the fraction of charged lipid in the vesicle is decreased, the fusion rate decreases but the fusion extent increases where the latter effect is probably due to reduced intervesicle electrostatic repulsion.
Quantification of the decay rate in multiple experiments showed significant decrease in fusion rates of NE alone and NE plus palmitate-stimulated cells.
Depletion of Trak1 in cells decreases mitochondrial fusion rate, resulting in a mitochondrial fragmentation phenotype with shorter and smaller mitochondria.
Overexpression of PINK1 led to a significant decrease in fusion rate (Fig. 5E).
Consistent with these studies performed in other cell types, we detected a shift to the shorter Opa1 forms in BA treated with NE, which may also explain the decrease in mitochondrial fusion rates.
