The emerging and diverse roles of bis(Monoacylglycero) phosphate lipids in cellular physiology and disease

Megan R. Showalter, Anastasia L. Berg, Alexander Nagourney, Hailey Heil, Kermit L. Carraway, Oliver Fiehn

Research output: Contribution to journalReview articlepeer-review

Abstract

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 sn-1:sn-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.

Original languageEnglish (US)
Article number8067
Pages (from-to)1-19
Number of pages19
JournalInternational journal of molecular sciences
Volume21
Issue number21
DOIs
StatePublished - Nov 1 2020

Keywords

  • Bis(monoacylglycero)phosphate
  • Lipidomics
  • Lysobisphophatidic acid
  • Lysosome

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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