Mitochondrial phospholipid transport: Role of contact sites and lipid transport proteins

One of the major constituents of mitochondrial membranes is the phospholipids, which play a key role in maintaining the structure and the functions of the mitochondria. However, mitochondria do not synthesize most of the phospholipids in situ, necessitating the presence of phospholipid import pathways. Even for the phospholipids, which are synthesized within the inner mitochondrial membrane (IMM), the phospholipid precursors must be imported from outside the mitochondria. Therefore, the mitochondria heavily rely on the phospholipid transport pathways for its proper functioning. Since, mitochondria are not part of a vesicular trafficking network, the molecular mechanisms of how mitochondria receive its phospholipids remain a relevant question. One of the major ways that hydrophobic phospholipids can cross the aqueous barrier of inter or intraorganellar spaces is by apposing membranes, thereby decreasing the distance of transport, or by being sequestered by lipid transport proteins (LTPs). Therefore, with the discovery of LTPs and membrane contact sites (MCSs), we are beginning to understand the molecular mechanisms of phospholipid transport pathways in the mitochondria. In this review, we will present a brief overview of the recent findings on the molecular architecture and the importance of the MCSs, both the intraorganellar and interorganellar contact sites, in facilitating the mitochondrial phospholipid transport. In addition, we will also discuss the role of LTPs for trafficking phospholipids through the intermembrane space (IMS) of the mitochondria. Mechanistic insights into different phospholipid transport pathways of mitochondria could be exploited to vary the composition of membrane phospholipids and gain a better understanding of their precise role in membrane homeostasis and mitochondrial bioenergetics.