Cell Biology

Eat Now

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Science  25 Oct 2013:
Vol. 342, Issue 6157, pp. 403
DOI: 10.1126/science.342.6157.403-a
CREDIT: C. T. CHU ET AL., NATURE CELL BIOLOGY 15 (15 SEPTEMBER 2013) © 2013 MACMILLIAN PUBLISHERS LIMITED

The daily wear and tear experienced by our cells can damage internal organelles, such as the mitochondria. The recognition and subsequent removal of injured mitochondria rely on a sequestration and engulfment process known as mitophagy, but the molecular pathways involved are unclear. Mitophagy plays a critical role in cellular health and in quality control, and its disruption has been implicated in neurodegeneration, diabetes, cardiac disease, and cancer. Working with cultured neuronal cells, Chu et al. now describe an “eat me” signal that identifies injured mitochondria as being fit for consumption by the intracellular recycling machinery. Cardiolipin is a mitochondria-specific phospholipid that normally resides within the inner mitochondrial membrane. The collapse of membrane asymmetry in mitochondria owing to damage inflicted by a variety of pro-mitophagy agents leads to the exposure of cardiolipin on the outer mitochondrial membrane, which marks them for delivery to lysosomes. The authors show that cardiolipin interacts with LC3, a protein known to be involved in autophagy; in particular, two arginine residues in the N-terminal region of LC3 stabilize the phosphate groups of cardiolipin, and subtracting the guanidinium side chains via mutation abrogated the binding of LC3. Thus, cells protect themselves from the potentially deleterious effects of damaged mitochondria by exploiting the damage-induced redistribution of cardiolipin.

Nat. Cell Biol. 15, 1197 (2013).

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