BEYOND LITTLE HANDSHAKE: ROLE OF PHOSPHOLIPIDS IN HEALTH AND DISEASE

Mohammad Owais, C. M. Gupta*

Analogous to the large sized protein and carbohydrate based macromolecules, the large macro-sized bio-membrane assemblies are primarily derived from the monomeric phospholipids (PL). Besides offering protection from outside environment, the PLs play important role in regulation of cellular structure, signalling, and various other related metabolic processes. In addition to regulating membrane integrity, curvature, and compartmentalization, they sustain architecture and function of various cellular organelles, such as mitochondria, where the major phospholipids namely phosphatidyl-ethanolamine  (PE) and cardiolipin (CL) are indispensable not only for cristae organization, however, also to play important role in the regulation of efficient oxidative phosphorylation as well. On the other hand, the phospholipids such as phosphatidylcholine (PC) are essential for lipoprotein assemblage and lipid transport, thereby linking membrane biogenesis to whole-body metabolic homeostasis. Beyond their structural roles, PLs function as central signalling platforms. They act as precursors of lipid-derived second messengers, orchestrate the spatial organization of membrane-associated protein complexes, and directly modulate the activity of enzymes and receptors. The phosphoinositides (PI) confer membrane identity and enable the precise recruitment of signalling proteins, while enzymatic remodelling of phospholipid headgroups and acyl chains generates bioactive mediators. Consequently, altered PL homeostasis has been implicated in cardiovascular and neurodegenerative diseases and more importantly in many types of cancer as well.  This review synthesizes current insights into the multifaceted roles of phospholipids in health and disease and also underscores significance of phospholipids in diagnostic biomarkers and therapeutic targets.