A detailed
lipid class analysis revealed that lysosomes from the brain, heart, and muscle – but not the liver
– exhibit an age-associated increase in bis(monoacylglycero)phosphates (BMPs) and
phosphatidylglycerols (PGs) (Fig. 3A). BMPs are unique lysosome-specific phospholipids
(87-90) that serve as co-factors for lysosomal enzymes (91, 92), facilitating the degradation of
other complex lipids, while PGs are their structural isomers (87). Increases in BMPs and BMPs/
PGs (representing isomeric BMPs or PGs that could not be distinguished) are particularly
pronounced in brain and heart lysosomes, with fewer significantly elevated species in muscle
(Fig. 3B). In contrast, the major lysosomal membrane phospholipids –phosphatidylcholines and
phosphatidylethanolamines – remain largely unchanged in aged lysosomes. This is consistent
with the notion that lysosomal yield was not increased in aged lysosome isolations and the
increase in BMPs is compositional (Fig. 3A and B).