Research Paper Volume 11, Issue 22 pp 10338—10355

GBA mutation promotes early mitochondrial dysfunction in 3D neurosphere models

Figure 7. Global summary of the observed molecular parameters in GBA mutant neurospheres. Compared to the controls, dysfunctional mitochondrial accumulation occurs in mutant GBA neurospheres under basal conditions, as shown by the accumulation of healthy and altered mitochondria, represented as elongated and rounded structures, respectively. Mitochondrial elimination is correct under mitophagy induction (CCCP) in the control line, as observed by the decrease of ATP, represented by the battery, and the macroautophagy induction, represented by the garbage bin. There is an impaired turnover of depolarized mitochondria under induced mitophagy in GBA neurospheres. This is not a result of impaired autophagosome formation and degradation, but at an earlier stage, where defective mitochondrial dysfunction was observed.