© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd doi:10.1111/tra.12230
Review
Phospholipid Synthesis and Transport in Mammalian Cells Jean E. Vance∗ Department of Medicine and Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, AB Canada ∗
Corresponding author: Jean E. Vance, [email protected]
Abstract Membranes of mammalian subcellular organelles contain defined
the ER (mitochondria-associated membranes, MAM) and decarboxy-
amounts of specific phospholipids that are required for normal func-
lated to phosphatidylethanolamine in mitochondria. Some evidence is
tioning of proteins in the membrane. Despite the wide distribution
presented suggesting that PS import into mitochondria occurs via mem-
of most phospholipid classes throughout organelle membranes, the
brane contact sites between MAM and mitochondria. Recent studies
site of synthesis of each phospholipid class is usually restricted to
suggest that protein complexes can form tethers that link two types of
one organelle, commonly the endoplasmic reticulum (ER). Thus, phos-
organelles thereby promoting lipid transfer. However, many questions
pholipids must be transported from their sites of synthesis to the
remain about mechanisms of inter-organelle phospholipid transport in
membranes of other organelles. In this article, pathways and subcellular
mammalian cells.
sites of phospholipid synthesis in mammalian cells are summarized. A single, unifying mechanism does not explain the inter-organelle transport of all phospholipids. Thus, mechanisms of phospholipid transport between organelles of mammalian cells via spontaneous membrane
Keywords endoplasmic reticulum, inter-organelle transport, lipid transfer proteins, membrane contact sites, mitochondria, mitochondria-associated membranes, phospholipids, plasma membrane
diffusion, via cytosolic phospholipid transfer proteins, via vesicles and
Received 4 September 2014, revised and accepted for publication
via membrane contact sites are discussed. As an example of the lat-
18 September 2014, uncorrected manuscript published online 22
ter mechanism, phosphatidylserine (PS) is synthesized on a region of
September 2014
The most abundant phospholipid in mammalian cells is phosphatidylcholine (PC). A variety of other phospholipids, including phosphatidylethanolamine (PE), phosphatidylserine (PS), sphingomyelin (SM), cardiolipin (CL), as well as phosphatidylinositol (PI) and its phosphorylated derivatives, are also important membrane constituents (Table 1). In addition to the phospholipids, other lipids such as cholesterol and glycosphingolipids are components of mammalian cell membranes. Yeast contain most of the same phospholipid classes that are present in mammalian cells but lack SM and cholesterol, although other sterols are present. Unlike mammalian cells, in which PC is the major phospholipid, Escherichia coli is devoid of PC, SM, PI
and cholesterol, whereas the most abundant phospholipid of this organism is PE. In addition, the outer membrane of this Gram-negative bacterium is composed primarily of lipopolysaccharides rather than phospholipids and contains the unique, complex lipid, lipid A. Although the lipid composition of E. coli membranes is profoundly different from that of mammalian cells, prokaryotic cells such as E. coli are able to perform many of the same basic functions that operate in mammalian cells. The actions of proteins that are embedded in membranes of eukaryotic cells depend critically on the membrane phospholipid composition (1). Different types of cells and www.traffic.dk 1
Vance
Table 1: Lipid composition of a typical nucleated mammalian cell Percentage of total lipidsa Phosphatidylcholine Phosphatidylethanolamine Phosphatidylinositol Phosphatidylserine Phosphatidic acid Sphingomyelin Cardiolipin Phosphatidylglycerol Glycosphingolipids Cholesterol a
45–55 15–25 10–15 5–10 1–2 5–10 2–5
Review
Phospholipid Synthesis and Transport in Mammalian Cells Jean E. Vance∗ Department of Medicine and Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, AB Canada ∗
Corresponding author: Jean E. Vance, [email protected]
Abstract Membranes of mammalian subcellular organelles contain defined
the ER (mitochondria-associated membranes, MAM) and decarboxy-
amounts of specific phospholipids that are required for normal func-
lated to phosphatidylethanolamine in mitochondria. Some evidence is
tioning of proteins in the membrane. Despite the wide distribution
presented suggesting that PS import into mitochondria occurs via mem-
of most phospholipid classes throughout organelle membranes, the
brane contact sites between MAM and mitochondria. Recent studies
site of synthesis of each phospholipid class is usually restricted to
suggest that protein complexes can form tethers that link two types of
one organelle, commonly the endoplasmic reticulum (ER). Thus, phos-
organelles thereby promoting lipid transfer. However, many questions
pholipids must be transported from their sites of synthesis to the
remain about mechanisms of inter-organelle phospholipid transport in
membranes of other organelles. In this article, pathways and subcellular
mammalian cells.
sites of phospholipid synthesis in mammalian cells are summarized. A single, unifying mechanism does not explain the inter-organelle transport of all phospholipids. Thus, mechanisms of phospholipid transport between organelles of mammalian cells via spontaneous membrane
Keywords endoplasmic reticulum, inter-organelle transport, lipid transfer proteins, membrane contact sites, mitochondria, mitochondria-associated membranes, phospholipids, plasma membrane
diffusion, via cytosolic phospholipid transfer proteins, via vesicles and
Received 4 September 2014, revised and accepted for publication
via membrane contact sites are discussed. As an example of the lat-
18 September 2014, uncorrected manuscript published online 22
ter mechanism, phosphatidylserine (PS) is synthesized on a region of
September 2014
The most abundant phospholipid in mammalian cells is phosphatidylcholine (PC). A variety of other phospholipids, including phosphatidylethanolamine (PE), phosphatidylserine (PS), sphingomyelin (SM), cardiolipin (CL), as well as phosphatidylinositol (PI) and its phosphorylated derivatives, are also important membrane constituents (Table 1). In addition to the phospholipids, other lipids such as cholesterol and glycosphingolipids are components of mammalian cell membranes. Yeast contain most of the same phospholipid classes that are present in mammalian cells but lack SM and cholesterol, although other sterols are present. Unlike mammalian cells, in which PC is the major phospholipid, Escherichia coli is devoid of PC, SM, PI
and cholesterol, whereas the most abundant phospholipid of this organism is PE. In addition, the outer membrane of this Gram-negative bacterium is composed primarily of lipopolysaccharides rather than phospholipids and contains the unique, complex lipid, lipid A. Although the lipid composition of E. coli membranes is profoundly different from that of mammalian cells, prokaryotic cells such as E. coli are able to perform many of the same basic functions that operate in mammalian cells. The actions of proteins that are embedded in membranes of eukaryotic cells depend critically on the membrane phospholipid composition (1). Different types of cells and www.traffic.dk 1
Vance
Table 1: Lipid composition of a typical nucleated mammalian cell Percentage of total lipidsa Phosphatidylcholine Phosphatidylethanolamine Phosphatidylinositol Phosphatidylserine Phosphatidic acid Sphingomyelin Cardiolipin Phosphatidylglycerol Glycosphingolipids Cholesterol a
45–55 15–25 10–15 5–10 1–2 5–10 2–5
