Fig. 1

L444P GBA heterozygous mutation leads to GBA abnormalities, accumulation of α-synuclein, and mitochondrial defects both in vitro and in vivo. a GBA enzymatic activities were measured using lysosome-enriched fraction samples of ventral midbrain (VMB) in WT or GBA^+/L444P mice. GBA enzyme activity was normalized against GBA enzyme activity of WT mice. b VMB lysates from WT and GBA^+/L444P were immunoblotted with anti-GBA and α-synuclein antibodies. c GBA and α-synuclein expression levels were normalized against β-actin. a, c Error bars represent the mean ± S.E.M (n = six mice per group). d Representative transmission electron microscopy (TEM) images of mitochondria in the SNpc of WT and GBA^+/L444P mice. e Mitochondrial length and f aspect ratio (mitochondrial major axis over minor axis) were measured from littermate WT control (sixty-four mitochondria from seven cells) and GBA^+/L444P mice (fifty mitochondria from seven cells) group and represented as graph. g Representative images of MitoTracker positive structure in WT and GBA^+/L444P primary cortical neurons (10 DIV). h The intensity of MitoTracker positive structure of WT and GBA^+/L444P primary cultured neurons (n = three mice per group). i Mitochondrial length and j aspect ratio (mitochondrial major axis over minor axis) are shown (thirty mitochondria from three different images of each group). k Reactive oxygen species (ROS) levels were measured in primary cortical neurons of WT and GBA^+/L444P using CM-H2DCFDA. l Mitochondrial complex I enzyme activity in WT and GBA^+/L444P primary cortical neurons. m, n Oxygen consumption rate (OCR) was determined by Seahorse assay in WT and GBA^+/L444P primary cortical neurons. k-n Error bars represent the mean ± S.E.M (n = six mice per group). Student’s t-test or *P < 0.05, **P < 0.01, ***P < 0.001 vs. WT group