*2.4.2 Membrane fluidity*

*Cell Growth*

gosome expansion [13, 14].

**2.2 Sphingolipids**

Another lipid component essential for autophagosome formation is PE [13, 14]. PE lipids present in the autophagosome are important for the ability of this structure to associate with Atg8, another essential autophagy protein. This is because successful recruitment of Atg8 to autophagosomes involves Atg8 lipidation to the head group of PE, ultimately yielding a mature autophagosome that is decorated by lipidated Atg8 [13, 14]. In fact, PE is the lipid that contributes the most to autopha-

The backbone of sphingolipids is not glycerol but sphingosine, an amino alcohol

Sphingolipids such as sphingosine-1-phosphate (S1P) and ceramides have been found to have an effect on autophagy [13, 14]. S1P, as part of its well-known role in fostering proliferation and cell survival, can induce autophagy in a way that engages elements usually associated with apoptosis [13, 14]. Ceramides, in their well-known role in promoting cell cycle arrest, promote cell death while engaging elements

Sterols are four-ringed steroid molecules that contain a hydroxyl functional group at position 3 and as well as a variety of potential side chains (**Figure 1C**) [10–12]. These lipids can be present in plant, animal, and microbial cells such as budding yeast. The predominant form of sterol lipid in animal cells is cholesterol. In other organisms, the lipid forms most similar to cholesterol in function are called by different names (**Figure 1C**). For example, the functional yeast equivalent of

Sterols in eukaryotes have been shown to influence specific forms of autophagy

The concept of membrane curvature refers to the lipid composition asymmetry between the two leaflets of a membrane bilayer [11, 15, 16]. The membrane curvature of an area can be changed, not only by altering its lipid composition, but also through the function of specialized proteins that can bind and remodel membranes. Early autophagosomes, often referred to as phagophores, have a high degree of curvature and are enriched for PI and PI3P [13, 14]. This combination of curvature

including chaperone-mediated autophagy (CMA), pexophagy (autophagy of peroxisomes) and lipophagy (autophagy of lipid droplets) [13, 14]. These types of specific autophagy are beyond the scope of this review and are therefore not

synthesized from palmitoyl-CoA and serine [10–12]. The covalent attachment of the sphingosine backbone to a fatty acid through an amide linkage yields an amphipathic sphingolipid (**Figure 1B**) [10–12]. Common examples of this type of lipid in cells include ceramides (the simplest form of sphingolipid), phosphosphingolipids (also known as sphingomyelins, the only phospholipids without a glycerol backbone), and glycosphingolipids [10–12]. The differences and diversity between these sphingolipids is dependent on the type of fatty acid and additional head groups attached to the sphingosine backbone. Sphingolipids were discovered and can be predominantly found in nervous tissue. This type of lipid can also be found

in lower eukaryotes such as budding yeast [10–12].

cholesterol is referred to as ergosterol (**Figure 1C**).

**2.4 Lipid contributions to membrane structure/function**

associated with autophagy [13, 14].

**2.3 Sterols**

discussed.

*2.4.1 Membrane curvature*

**88**

Membrane fluidity refers to the ability of a membrane to sustain diffusiondriven movement of molecules within it [11, 17]. In membranes, diffusion takes place laterally [11, 15, 17]. The presence of unsaturated and sterol lipid structures enhances membrane fluidity, ultimately allowing for more lateral diffusion of molecules and rendering it easier to bend and deform [11, 17].

This relationship between membrane fluidity and bending is highly relevant to autophagosome membranes [13, 14]. Early autophagosomal structures are characterized by high levels of curvature, suggesting that fluidity is key for autophagosome formation [13, 14]. In fact, autophagosomes are enriched for unsaturated lipids, and abrogation of enzyme functions that mediate desaturation can have inhibitory effects on autophagy [13, 14].
