Fatty Acid Trafficking in Starved Cells: Regulation by Lipid Droplet Lipolysis, Autophagy, and Mitochondrial Fusion Dynamics

 http://www.sciencedirect.com/science/article/pii/S1534580715000726

 Angelika S. Rambold, Sarah Cohen and Jennifer Lippincott-Schwartz

Under nutrient starvation, fatty acids (FAs), which are often stored in lipid droplets, move into mitochondria to drive beta oxidation-based metabolism to sustain energy levels. Exactly how FA become mobilized and delivered into mitochondria is unclear. In this paper they investigate which mechanisms are used to release FAs into the cytoplasm and how FAs move into mitochondria.

They find that FAs are mainly released from lipid droplets by lipolysis (as opposed to lipophagy).

In starved MEFs, almost all lipid droplets were closely associated with mitochondria and this allows FAs to move directly from the lipid droplets into mitochondria. Mitochondria were also highly fused in the starved cells, enabling equilibration of FAs throughout the mitochondrial population. In cells with fusion deficiencies (through knockout of Mfn1 or Opa1), many mitochondrial elements were not close to lipid droplets and FAs did not become homogeneously distributed across the mitochondrial population.

In starved wild-type cells, a rapid increase in FA oxidation was seen, and cells could almost maintain total mitochondrial respiration levels over the entire starvation period (24 hours). Mfn1 knockout cells initially showed an increase in FA oxidation but within 24 hours FA oxidation reduced significantly, causing total mitochondrial respiration levels to drop over time.

It is suggested that delivery of FAs to mitochondria occurs at limited sites, only there where lipid droplets are in close proximity to mitochondria. This may explain why lipid droplets and mitochondria are so closely associated. Having too many free FAs in the cytoplasm can cause damage, so efficient movement of FAs from the droplets into mitochondria is beneficial. Having mitochondria all fused up then enables the FAs to distribute themselves homogeneously throughout the mitochondrial population.