Lipid Metabolism Dynamics in Cellular Systems

Lipid metabolism dynamics span the synthesis, trafficking and utilisation of lipids within cells. Central to energy storage and membrane maintenance, lipids are shuttled between organelles, reorganised in response to nutrient levels and modulated by biosynthetic and catabolic pathways. Triacylglycerols accumulate in cytosolic lipid droplets, while phospholipids and sterols incorporate into membranes. Coordinated interactions among the endoplasmic reticulum, lipid droplets and mitochondria regulate lipid flux through enzymatic networks and contact sites. Recent advances have uncovered alternative biosynthetic enzymes, dynamic organelle interplay under stress and the molecular sensors that tune lipid catabolism. These insights illuminate the mechanisms by which cells maintain homeostasis and adapt to metabolic challenges, with implications for obesity, cardiovascular disease and metabolic disorders.

Research from Nature Portfolio

Recent studies have unveiled an alternative triglyceride biosynthesis pathway in human cells driven by an acyltransferase termed DIESL and regulated by TMX1 at endoplasmic reticulum contact sites. This system operates independently of classical DGAT enzymes to sustain mitochondrial function during lipid scarcity and support rapid postnatal growth in animal models. Additional work delineates how energy stress activates AMPK to remodel detyrosinated microtubules, promoting dispersion of lipid droplets towards cell peripheries and enhancing their contacts with mitochondria for efficient β-oxidation under starvation.

Lipid Metabolism Dynamics in Cellular Systems publication trend

The graph below shows the total number of articles in lipid metabolism dynamics in cellular systems across all publications each year (not limited to Nature Index journals).

Technical terms

Lipid droplet (LD): A cytosolic organelle composed of a neutral lipid core enclosed by a phospholipid monolayer, serving as a storage depot for triacylglycerols and sterol esters.

Triacylglycerol (TAG): A neutral lipid formed by esterification of three fatty acids to glycerol, representing the primary energy reserve within lipid droplets.

β-oxidation: The mitochondrial process that sequentially cleaves fatty acid chains to generate acetyl-CoA, NADH and FADH₂ for ATP production.

Endoplasmic reticulum (ER): A membranous network in eukaryotic cells, central to lipid and protein synthesis, and a primary site for lipid droplet biogenesis.

AMP-activated protein kinase (AMPK): A cellular energy sensor kinase that responds to changes in the AMP:ATP ratio, orchestrating metabolic pathway adjustments under stress.

DIESL: A recently identified diacylglycerol acyltransferase-like enzyme that catalyses an alternative pathway of triglyceride synthesis at ER contact sites.

TMX1: An endoplasmic reticulum-resident oxidoreductase that binds and regulates DIESL activity, modulating lipid droplet formation under metabolic stress.

References

1. Identification of an alternative triglyceride biosynthesis pathway. Nature (2023).
2. Burst of hopping trafficking correlated reversible dynamic interactions between lipid droplets and mitochondria under starvation. Exploration (2023).
3. Thematic Review Series: Glycerolipids. DGAT enzymes and triacylglycerol biosynthesis. Journal of Lipid Research (2008).
4. AMPK activation promotes lipid droplet dispersion on detyrosinated microtubules to increase mitochondrial fatty acid oxidation. Nature Communications (2015).