Loss of Peter Pan (PPAN) Affects Mitochondrial Homeostasis and Autophagic Flux
Abstract
:1. Introduction
2. Materials and Methods
2.1. Plasmids and siRNAs
- si control: GCUACCUGUUCCAUGGCCA
- si PPAN-B: GGACGAUGAUGAACAGGAA
- Custom siRNAs were obtained from Thermo Scientific and si PPAN-A was from Qiagen (FlexiTube siRNA #SI00125545).
2.2. Antibodies, Dyes and Drugs
2.3. Cell Culture, Transfections and Drug Treatments
2.4. Cell Lysates, Western Blots and Densitometry
2.5. Mitochondria Isolation and Proteinase K Treatment
2.6. Isolation of Recombinant Proteins and Lipid Binding Assay
2.7. Immunofluorescence
2.8. qPCR Expression Analysis
- PPAN-fw: 5-CGCCCAGGGAAGAGAGT-3
- PPAN-rv: 5-GAAACCGAGGGCCACATC-3
- GAPDH-fw: 5-TGGTCTCCTCTGACTTCAAC-3
- GAPDH-rv: 5-CGTTGTCATACCAGGAAATGAG-3
2.9. mtDNA Assay
2.10. Image Acquisition and Cell Counting
2.11. Transmission Electron Microscopy
2.12. Oxygraph Assay
2.13. ATP, ADP and AMP Measurements
2.14. Citrate Synthase Measurements
2.15. Statistical Analysis
3. Results
3.1. PPAN Interacts with Cardiolipin and Controls Mitochondrial Homeostasis
3.2. PPAN Knockdown Enhances Basal Autophagy in HeLa Cells
3.3. PPAN Knockdown Enhances Starvation-Induced Autophagic Flux in HeLa Cells
3.4. PPAN Knockdown Enhances Basal Autophagic Flux in HEK293A GFP-LC3 Cells
3.5. PPAN Knockdown Leads to Accumulation of the Mitophagy Machinery at Mitochondria in Parkin-Expressing HeLa Cells
3.6. PPAN is Decreased by CCCP and PPAN Knockdown Further Decreases Mitochondrial Mass in Parkin-Expressing Cells
3.7. PPAN Knockdown Decreases Mitochondrial Mass and mtDNA to Nuclear DNA Ratio in U2OS Cells
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Dannheisig, D.P.; Beck, E.; Calzia, E.; Walther, P.; Behrends, C.; Pfister, A.S. Loss of Peter Pan (PPAN) Affects Mitochondrial Homeostasis and Autophagic Flux. Cells 2019, 8, 894. https://doi.org/10.3390/cells8080894
Dannheisig DP, Beck E, Calzia E, Walther P, Behrends C, Pfister AS. Loss of Peter Pan (PPAN) Affects Mitochondrial Homeostasis and Autophagic Flux. Cells. 2019; 8(8):894. https://doi.org/10.3390/cells8080894
Chicago/Turabian StyleDannheisig, David P., Eileen Beck, Enrico Calzia, Paul Walther, Christian Behrends, and Astrid S. Pfister. 2019. "Loss of Peter Pan (PPAN) Affects Mitochondrial Homeostasis and Autophagic Flux" Cells 8, no. 8: 894. https://doi.org/10.3390/cells8080894