Parkin restrictions for damaged mitochondria

Cdc14 in good repair C dc14 is an essential regulator of the yeast cell cycle, but its vertebrate homologues appear to be surprisingly dispensable, Mocciaro et al. report. They are required for effi cient DNA repair, however. Yeast Cdc14 is a phosphatase that counteracts the cyclin-dependent kinases to control many aspects of the cell cycle including mitotic exit. Vertebrates have at least two versions of the phosphatase that have a similarly wide range of functions according to overexpression and depletion experiments. Cdc14A is thought to control centrosome splitting and cytokinesis, for example, while Cdc14B promotes mitotic exit and activates a DNA damage checkpoint that maintains cells in G2. Mocciaro et al. were thus surprised to fi nd that deleting either phosphatase from chicken DT40 cells had no obvious effect on cell viability or proliferation. And irradiated cells lacking Cdc14A or Cdc14B still arrested in G2. But the knockout cells took longer to repair the radiation-induced DNA damage. Even without irradiation, cells lacking Cdc14A or Cdc14B had higher background levels of double-strand breaks, indicating that the phosphatases are needed to effi ciently mend DNA damage. This function isn't unique to chicken cells because genetically deleting either Cdc14 homologue from human cells also slowed DNA repair. Human cells lacking Cdc14A or Cdc14B were also viable and passed through the cell cycle without any problems. Although the two isoforms localize to different parts of the cell, it's possible that they redundantly carry out the functions of Cdc14 indicated by previous experiments. The authors now plan to test this by generating double knockout cell lines. M utations that cause Parkinson's disease prevent cells from destroying defective mi-tochondria, Lee et al. report. Defects in the ubiquitin ligase Parkin are linked to early-onset cases of this neu-rodegenerative disorder. The wild-type protein promotes the removal of impaired mi-tochondria by a specialized version of the autophagy pathway called mitophagy, delivering mitochondria to the lysosomes for degradation. Mitochondria are often dysfunctional in Parkinson's disease, but how Parkin stimulates mitophagy and whether the pathway goes wrong during pathogenesis is unknown. Lee et al. found that cells expressing mutant forms of Parkin failed to clear their mitochondria after the organelles were damaged. Different mutations blocked mitophagy at distinct steps: mitochondria accumulated in the perinuclear region of cells expressing Parkin lacking its ubiquitin ligase activity, for example. The researchers found that ubiquitina-tion of defective mitochondria by Parkin normally recruits the autophagy proteins …