Research ArticleCell Biology

The E3 ligase PARC mediates the degradation of cytosolic cytochrome c to promote survival in neurons and cancer cells

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Science Signaling  15 Jul 2014:
Vol. 7, Issue 334, pp. ra67
DOI: 10.1126/scisignal.2005309

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Putting the PARC’ing Break on Cell Death

Release of cytochrome c (Cyt c) from the mitochondria in response to cell stress or mitochondrial damage triggers cell death. Cancer cells and cells that have ceased dividing, such as neurons, can be less susceptible to Cyt c–induced cell death. The inability of neurons to cope with mitochondrial stress or damage contributes to some neurodegenerative diseases. Gama et al. induced mitochondrial stress in cultures of human glioma or neuroblastoma cell lines and in cultures of sympathetic neurons from mice and found that the E3 ligase PARC ubiquitylated cytosolic Cyt c, inducing its degradation. Cyt c accumulated in PARC-deficient cells, and mitochondrial stress produced an increased cell death response in these cells. The findings indicate that PARC may be important for promoting neuronal survival in diseases associated with mitochondrial damage and might be therapeutically targeted to enhance the cytotoxicity of cancer treatments.