Within human bone marrow two million neutrophils are generated every second which require complex regulation and substantial bio-energy. The mechanisms that govern these are not yet fully understood.
Researchers at the Kennedy Institute have found that autophagy can degrade lipid droplets in neutrophil precursors to generate the large amounts of molecular energy-currency (adenosine triphosphate) required to sustain differentiation. By breaking down lipid droplets into free fatty acids, autophagy fuels a respiration pathway in the mitochondria, the energy-producing factories of cells, to enable differentiation.
In line with this, researchers found defects in the autophagy pathway associated with acute myeloid leukaemia, a disease that is characterised by immature myeloid precursors which are blocked in their differentiation.
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- Autophagy-Dependent Generation of Free Fatty Acids Is Critical for Normal Neutrophil Differentiation: Thomas Riffelmacher, Alexander Clarke, Felix C. Richter, Amanda Stranks, Sumeet Pandey, Sara Danielli, Philip Hublitz, Zhanru Yu, Errin Johnson, Tobias Schwerd, James McCullagh, Holm Uhlig, Sten Eirik W. Jacobsen, Anna Katharina Simon.
The next goal for the researchers is to test if we can exploit this autophagy pathway to overcome the differentiation block in myeloid leukemia.