GBA1 deficiency leads to glucosylceramide accumulation in the inner mitochondrial membrane (as shown by lipidomics of patient fibroblasts), which directly stabilizes Miro1 protein levels by inhibiting the mitochondrial protease LONP1. Miro1 is a calcium-sensitive adaptor that tethers mitochondria to the microtubule motor complex; under normal conditions, Miro1 is ubiquitinated by the Pink1-Parkin pathway and degraded to enable mitophagosome formation. When GlcCer stabilizes Miro1, damaged mitoch
Radar Chart — 10 Dimensions
Score Comparison Bars
Mechanistic
0.74
Evidence
0.68
Novelty
0.82
Feasibility
0.00
Impact
0.00
Druggability
0.00
Safety
0.00
Competition
0.00
Data
0.00
Reproducible
0.00
KG Connect
0.19
Score Breakdown
Dimension
GBA1-Deficiency Disrupts Mitoc
Mechanistic
0.740
Evidence
0.680
Novelty
0.820
Feasibility
0.000
Impact
0.000
Druggability
0.000
Safety
0.000
Competition
0.000
Data
0.000
Reproducible
0.000
KG Connect
0.187
Evidence
GBA1-Deficiency Disrupts Mitochondrial- Lysosomal Contact Si