Dannheisig 2019 Cells

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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.

» PMID: 31416196 Open Access

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 O2k-Network Lab: DE Ulm Radermacher P

Labels: MiParea: Respiration, Genetic knockout;overexpression 

Stress:Cell death  Organism: Human  Tissue;cell: HeLa  Preparation: Permeabilized cells, Intact cells 

Coupling state: LEAK, ROUTINE, ET  Pathway: N, S, CIV, NS, ROX  HRR: Oxygraph-2k 

Labels, 2019-08