Cell Biology

Selective Consumption

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Science  05 Feb 2010:
Vol. 327, Issue 5966, pp. 625
DOI: 10.1126/science.327.5966.625-c

Degeneration of photereceptor neurons in Drosophila.

CREDIT: LEE ET AL., EMBO J. 29, 10.1038/EMBOJ.2009.405 (2010)

Cellular self-digestion, or macroautophagy, occurs when the cell degrades its internal components. This helps to avoid the accumulation of potentially toxic protein aggregates, which leads to neurodegenerative diseases, and it serves to recycle nutrients during starvation. A membrane-bound organelle—the autophagosome—sequesters the intracellular material to be degraded, and it subsequently fuses with lysosomes, which provide hydrolytic enzymes.

Lee et al. have identifed a differential requirement for the histone deacetylase HDAC6 in starvation-dependent versus -independent macroautophagy. HDAC6 binds F-actin and microtubules and was previously found to play a role in clearing misfolded proteins from the cell. The authors found that HDAC6 promotes fusion between autophagosomes and lysosomes by recruiting a network of F-actin. Both HDAC6 and F-actin were required for proper protein clearance, and HDAC6-deficient mice and Drosophila exhibited increased protein aggregation in neurons, as well as symptoms of neurodegeneration. However, neither HDAC6 nor F-actin was required for the fusion of autophagosomes and lysosomes during starvation, indicating that protein and organelle degradation is selective, targeting only damaged or potentially toxic substrates.

EMBO J. 29, 10.1038/emboj.2009.405 (2010).

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