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Analysis of neuronal phosphoproteome reveals PINK1 regulation of BAD function and cell death

Cell Death & Differentiationvolume 25pages904917 (2018) | Download Citation


PINK1 mutations that disrupt its kinase activity cause autosomal recessive early onset Parkinson’s disease (PD). Although research in recent years has elucidated a PINK1-Parkin pathway of mitophagy activation that requires PINK1 kinase activity, mitophagy-independent functions of PINK1 and their possible roles in PD pathogenesis have been proposed. Using an unbiased quantitative mass spectrometry approach to analyze the phosphoproteome in primary neurons from wild type and Pink1 knockout mice after mitochondrial depolarization, we uncovered PINK1-regulated phosphorylation sites, which involve coordinated activation of multiple signaling pathways that control cellular response to stress. We further identified the pro-apoptotic protein BAD as a potential mitochondrial substrate of PINK1 both in vitro and in vivo, and found that cells more susceptible to a12poptosis induced by mitochondrial damage can be rescued by phosphorylation mimic BAD. Our results thus suggest that PINK1 kinase activity is important for pro-apoptotic protein function in regulation of cell death.

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The authors would like to acknowledge financial support from the Shanghai Pujiang Talent Project (14PJ1402900), and ECNU National “985” Project grant.

Author's contributions

LL, ZZ, and LX conceived the project; HW, QZ performed the experiments. BT, HW, and LL analyzed data; LL, BT, and HW wrote the paper.

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Author notes

  1. Edited by N. Chandel


  1. Key Laboratory of Brain Functional Genomics of Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, and Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, China

    • Huida Wan
    • , Bin Tang
    • , Qiufang Zeng
    •  & Lujian Liao
  2. Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, China

    • Xun Liao
  3. Institute of Precision Medicine, State key laboratory of Medical Genetics, the Xiangya Hospital and the Xiangya Medical School, Central South University, Changsha, Hunan, 410078, China

    • Zhuohua Zhang


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The authors declare that they have no competing interests.

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Correspondence to Bin Tang or Lujian Liao.

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