Formation and Regulation of Mitochondrial Membranes

Mitochondrial membrane phospholipids are essential for the mitochondrial architecture, the activity of respiratory proteins, and the transport of proteins into the mitochondria. The accumulation of phospholipids within mitochondria depends on a coordinate synthesis, degradation, and trafficking of phospholipids between the endoplasmic reticulum (ER) and mitochondria as well as intramitochondrial lipid trafficking. Several studies highlight the contribution of dietary fatty acids to the remodeling of phospholipids and mitochondrial membrane homeostasis. Understanding the role of phospholipids in the mitochondrial membrane and their metabolism will shed light on the molecular mechanisms involved in the regulation of mitochondrial function and in the mitochondrial-related diseases. 1. Introduction Mitochondria are involved in a wide range of cellular processes of importance for cell survival. The inner mitochondrial membrane is the active site for the electron transport chain and ATP production. Its integrity is crucial for mitochondrial function and depends on the supply of proteins and phospholipids. As one of the major classes of lipids in the lipid bilayer of cell and organelle membranes, phospholipids are responsible for maintaining both the structural integrity of a cell and spatial separation of subcellular compartments. The major classes of phospholipids found in the mitochondrial membrane are similar to other membranes such as phosphatidylcholine (PC) and phosphatidylethanolamine (PE), and some are exclusively components of mitochondrial membrane such as cardiolipin (CL) [1]. The interaction between phospholipids and proteins is important particularly in the inner mitochondrial membrane. A significant proportion of inner membrane-associated proteins are comprised of proteins involved in the oxidative phosphorylation and their activity depends on the phospholipid composition of the membrane. Changes in the phospholipid composition can affect mitochondrial respiration [2], which has been linked to a variety of human diseases such as Barth syndrome, ischemia, and heart failure [3, 4]. The phospholipid diversity in the mitochondrial membrane is also influenced by variation in length and degree of unsaturation of fatty acyl chain present within each class of phospholipid [5]. However the role of acyl chain composition of phospholipids in mitochondrial function is still poorly understood. The maintenance of the phospholipid composition in the mitochondrial membranes is essential for mitochondrial function, structure, and biogenesis and relies on the