Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis, autophagy and mitochondrial fusion dynamics

By Angelika S. Rambold, Sarah Cohen, Jennifer Lippincott-Schwartz. Developmental Cell, 2015

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Summary Fatty acids (FAs) provide cellular energy under starvation, yet how they mobilize and move into mitochondria in starved cells, driving oxidative respiration, is unclear. Here, we clarify this process by visualizing FA trafficking with a fluorescent FA probe. The labeled FA accumulated in lipid droplets (LDs) in well-fed cells, but moved from LDs into mitochondria when cells were starved. Autophagy in starved cells replenished LDs with FAs, increasing LD number over time. Cytoplasmic lipases removed FAs from LDs, enabling their transfer into mitochondria. This required mitochondria to be highly fused and localized near LDs. When mitochondrial fusion was prevented in starved cells, FAs neither homogeneously distributed within mitochondria nor became efficiently metabolized. Instead, FAs re-associated with LDs and fluxed into neighboring cells. FAs thus engage in complex trafficking itineraries regulated by cytoplasmic lipases, autophagy and mitochondrial fusion dynamics, ensuring maximum oxidative metabolism and avoidance of FA toxicity in starved cells.

Subfields: Biochemistry, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/69451958fb8bdd1d0274aaf0d6340e89568c7bc1