Dannheisig 2019 Cells
| Dannheisig DP, Beck E, Calzia E, Walther P, Behrends C, Pfister AS (2019) Loss of Peter Pan (PPAN) affects mitochondrial homeostasis and autophagic flux. Cells 8:E894. |
Dannheisig DP, Beck E, Calzia E, Walther P, Behrends C, Pfister AS (2019) Cells
Abstract: Nucleolar stress is a cellular response to inhibition of ribosome biogenesis or nucleolar disruption leading to cell cycle arrest and/or apoptosis. Emerging evidence points to a tight connection between nucleolar stress and autophagy as a mechanism underlying various diseases such as neurodegeneration and treatment of cancer. Peter Pan (PPAN) functions as a key regulator of ribosome biogenesis. We previously showed that human PPAN localizes to nucleoli and mitochondria and that PPAN knockdown triggers a p53-independent nucleolar stress response culminating in mitochondrial apoptosis. Here, we demonstrate a novel role of PPAN in the regulation of mitochondrial homeostasis and autophagy. Our present study characterizes PPAN as a factor required for maintaining mitochondrial integrity and respiration-coupled ATP production. PPAN interacts with cardiolipin, a lipid of the inner mitochondrial membrane. Down-regulation of PPAN enhances autophagic flux in cancer cells. PPAN knockdown promotes recruitment of the E3-ubiquitin ligase Parkin to damaged mitochondria. Moreover, we provide evidence that PPAN knockdown decreases mitochondrial mass in Parkin-expressing cells. In summary, our study uncovers that PPAN knockdown is linked to mitochondrial damage and stimulates autophagy. • Keywords: PPAN, Parkin, Wnt target, Apoptosis, Autophagy, Mitochondria, Mitophagy, Nucleolar stress, Nucleolus, Ribosome • Bioblast editor: Plangger M
Labels: MiParea: Respiration
HRR: Oxygraph-2k
Labels, 2019-08
