FIGURE 6.

Potential consequences of the absence of SERAC1 activity. (A) PG that is generated on the matrix-leaflet of the IMM is trafficked out of the mitochondrion and remodeled by SERAC1 on the ER MAMs. Remodeled PG can subsequently serve as substrate for BMP and CL synthesis. BMP in the endosomsal/lysosomal compartments regulates (green arrow) cholesterol esterification and trafficking out of the compartment. (B) In the absence of a functional SERAC1, PG is not remodeled and accumulates shorter acyl chain moieties. The decrease in acyl chain length somehow reduces overall BMP levels, perhaps because the unremodeled PG is a poor precursor for BMP synthesis. Reduced BMP levels in the endosome/lysosome impairs cholesterol esterification (inhibition in red) and leads to decreased (red arrows) cholesterol efflux. The lack of SERAC1 also changes the steady state composition of CL acyl chains. Blue arrows denote enzymatic reactions and lipid movements. Dashed arrows describe uncharacterized steps and pathways.