Phospholipids: Identification and Implication in Muscle Pathophysiology

Abstract

Phospholipids (PLs) are amphiphilic molecules that were essential for life to become cellular. PLs have not only a key role in compartmentation as they are the main components of membrane, but they are also involved in cell signaling, cell metabolism, and even cell pathophysiology. Considered for a long time to simply be structural elements of membranes, phospholipids are increasingly being viewed as sensors of their environment and regulators of many metabolic processes. After presenting their main characteristics, we expose the increasing methods of PL detection and identification that help to understand their key role in life processes. Interest and importance of PL homeostasis is growing as pathogenic variants in genes involved in PL biosynthesis and/or remodeling are linked to human diseases. We here review diseases that involve deregulation of PL homeostasis and present a predominantly muscular phenotype.

Keywords: disease; endoplasmic reticulum; mass spectrometry; membrane; mitochondria; muscle; phospholipids.

Figure 2

FA nomenclature. The chemical structure of FA showing the physiological numbering (black), the first double bond being at the third or sixth carbon from the omega start, and the chemical numbering (red) with conventions for the double bond location (E in cis, Z in trans). One of numerous possibilities of 3D representation was obtained thanks to Molview [11]. 3D structure is influenced by local environments such as pH.

Figure 1

The great diversity of phospholipids.

Figure 3

TIC (total ion chromatogram) by MS ESI-neg profiling and Corona CAD analysis for phospholipid class detection. Standard analysis of 0.3 g/L of PA, PG, CL, PI, PE, PS, LPE, PC, SM, and LPC.

Figure 4

Diacylglycerol (DAG) and CDP-DAG are two key elements in PL biosynthesis. GPAT: glycerol-3-phosphate acyltransferase, LPAAT: lysophosphatidic acid acyltransferases, PAP: phosphatidic acid phosphatases, DGK: diacylglycerol kinase, CDS: CDP-DAG synthetase, DAGAT: diacylglycerol acyl transferase, ALCAT1: AcylCoA:lysoCL acyltransferase 1, MLCAT1: monolysoCL acyltransferase 1, TAZ: tafazzin, EK: ethanolamine kinase, ET: CTP:phosphoethanolamine PE cytidylyltransferase, EPT: ethanolaminephosphotransferase, PSD: phosphatidylserine decarboxylase, PSS2: phosphatidylserine synthase 2, CK: choline kinase, CT: CTP: phosphocholine cytidylyltransferase, CPT: cholinephosphotransferase, PSS1: phosphatidylserine synthase 1, SMS: sphingomyelin synthase.