NIH West Coast Metabolomics Center, University of California Davis, Davis, CA 95616, USA.
Department of Biochemistry and Molecular Medicine, UC Davis School of Medicine, Sacramento, CA 95817, USA.
Int J Mol Sci. 2020 Oct 29;21(21):8067. doi: 10.3390/ijms21218067.
Although understudied relative to many phospholipids, accumulating evidence suggests that bis(monoacylglycero)phosphate (BMP) is an important class of regulatory lipid that plays key roles in lysosomal integrity and function. BMPs are rare in most mammalian tissues, comprising only a few percent of total cellular lipid content, but are elevated in cell types such as macrophages that rely heavily on lysosomal function. BMPs are markedly enriched in endosomal and lysosomal vesicles compared to other organelles and membranous structures, and their unique -1:-1' stereoconfiguration may confer stability within the hydrolytic lysosomal environment. BMP-enriched vesicles serve in endosomal-lysosomal trafficking and function as docking structures for the activation of lysosomal hydrolytic enzymes, notably those involved in the catabolic breakdown of sphingolipids. BMP levels are dysregulated in lysosomal storage disorders, phospholipidosis, metabolic diseases, liver and kidney diseases and neurodegenerative disorders. However, whether BMP alteration is a mediator or simply a marker of pathological states is unclear. Likewise, although BMP acyl chain composition may be altered with disease states, the functional significance of specific BMP species remains to be resolved. Newly developed tools for untargeted lipidomic analysis, together with a deeper understanding of enzymes mediating BMP synthesis and degradation, will help shed further light on the functional significance of BMPs in cellular physiology and pathology.
虽然与许多磷脂相比，双（单酰甘油）磷酸（BMP）的研究相对较少，但越来越多的证据表明，BMP 是一类重要的调节性脂质，在溶酶体完整性和功能中发挥关键作用。BMP 在大多数哺乳动物组织中含量很少，仅占总细胞脂质含量的百分之几，但在依赖溶酶体功能的细胞类型（如巨噬细胞）中含量升高。BMP 在内涵体和溶酶体小泡中比其他细胞器和膜结构丰富得多，其独特的-1:-1'立体构型可能在水解溶酶体环境中赋予其稳定性。富含 BMP 的小泡在内涵体-溶酶体运输中起作用，并作为溶酶体水解酶激活的 docking 结构，特别是那些参与鞘脂分解代谢的酶。BMP 水平在溶酶体贮积病、磷脂病、代谢疾病、肝和肾病以及神经退行性疾病中失调。然而，BMP 的改变是病理状态的介质还是仅仅是标记物尚不清楚。同样，尽管 BMP 酰基链组成可能因疾病状态而改变，但特定 BMP 种类的功能意义仍有待解决。新开发的非靶向脂质组学分析工具，以及对介导 BMP 合成和降解的酶的更深入了解，将有助于进一步阐明 BMP 在细胞生理学和病理学中的功能意义。
