The Role of Phospholipid Alterations in Mitochondrial and Brain Dysfunction after Cardiac Arrest

Abstract

The human brain possesses three predominate phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS), which account for approximately 35-40%, 35-40%, and 20% of the brain's phospholipids, respectively. Mitochondrial membranes are relatively diverse, containing the aforementioned PC, PE, and PS, as well as phosphatidylinositol (PI) and phosphatidic acid (PA); however, cardiolipin (CL) and phosphatidylglycerol (PG) are exclusively present in mitochondrial membranes. These phospholipid interactions play an essential role in mitochondrial fusion and fission dynamics, leading to the maintenance of mitochondrial structural and signaling pathways. The essential nature of these phospholipids is demonstrated through the inability of mitochondria to tolerate alteration in these specific phospholipids, with changes leading to mitochondrial damage resulting in neural degeneration. This review will emphasize how the structure of phospholipids relates to their physiologic function, how their metabolism facilitates signaling, and the role of organ- and mitochondria-specific phospholipid compositions. Finally, we will discuss the effects of global ischemia and reperfusion on organ- and mitochondria-specific phospholipids alongside the novel therapeutics that may protect against injury.

Keywords: cardiac arrest; fatty acids; ischemia; lysophospholipids; phospholipids.

Figure 1

Diagram of phospholipid structure and classification. This diagram illustrates the basic structural features of fatty acids, distinguishing features of phospholipids and lysophospholipids, and provides relevant examples of head groups and major fatty acid chains.

Figure 2

Schematic of phospholipid biosynthesis in the mitochondria. This schematic outlines the importation patterns of precursor phospholipids into the mitochondria, the biosynthetic pathways responsible for converting them into other phospholipids, and the role of cardiolipin in facilitating phospholipid remodeling.