BLOC-1 and BORC: Complex regulators of endolysosomal dynamics

Endolysosomes are dynamic organelles that undergo movement along the cytoskeleton, fusion, fission, and tubulation during their lifetime. These processes are regulated by complex molecular machineries, including the structurally related hetero-octameric complexes BLOC-1 and BORC. BLOC-1 associates with early endosomes to mediate the biogenesis of lysosome-related organelles (LROs), such as melanosomes and platelet dense bodies. Accordingly, mutations in BLOC-1 subunits cause Hermansky-Pudlak syndrome (HPS), a disorder characterized by pigmentation defects and bleeding abnormalities. In contrast, BORC associates with lysosomes, late endosomes, and synaptic vesicle precursors, promoting their transport along microtubules. BORC also regulates endolysosome fusion with other endolysosomes, as well as with phagosomes and autophagosomes. Mutations in BORC subunits cause a severe neurodevelopmental disorder in humans. In this article, we review recent progress in the elucidation of the structure, evolution, physiological roles, and regulation of BLOC-1 and BORC, highlighting their critical contributions to maintaining endolysosomal organization and function.