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The Paf1 complex transcriptionally regulates the mitochondrial-anchored protein Atg32 leading to activation of mitophagy

Zheng, L., Shu, W-J., Li, Y-M., Mari, M., Yan, C., Wang, D., Yin, Z-H., Jiang, W., Zhou, Y., Okamoto, K., Reggiori, F., Klionsky, D. J., Song, Z. & Du, H-N., 19-Sep-2019, In : Autophagy. 16, 8, p. 1366-1379 14 p.

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  • The Paf1 complex transcriptionally regulates the mitochondrial anchored protein Atg32 leading to activation of mitophagy

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DOI

  • Liangde Zheng
  • Wen-Jie Shu
  • Yu-Min Li
  • Muriel Mari
  • Chaojun Yan
  • Dehe Wang
  • Zhao-Hong Yin
  • Wei Jiang
  • Yu Zhou
  • Koji Okamoto
  • Fulvio Reggiori
  • Daniel J Klionsky
  • Zhiyin Song
  • Hai-Ning Du

Mitophagy is a critical process that safeguards mitochondrial quality control in order to maintain proper cellular homeostasis. Although the mitochondrial-anchored receptor Atg32-mediated cargo-recognition system has been well characterized to be essential for this process, the signaling pathway modulating its expression as a contribution of governing the mitophagy process remains largely unknown. Here, bioinformatics analyses of epigenetic or transcriptional regulators modulating gene expression allow us to identify the Paf1 complex (the polymerase-associated factor 1 complex, Paf1C,) as a transcriptional repressor of ATG genes. We show that Paf1C suppresses glucose starvation-induced autophagy, but does not affect nitrogen starvation- or rapamycin-induced autophagy. Moreover, we show that Paf1C specifically regulates mitophagy through modulating ATG32 expression. Deletion of the genes encoding two core subunits of Paf1C, Paf1 and Ctr9, increases ATG32 and ATG11 expression and facilitates mitophagy activity. Although Paf1C is required for many histone modifications and gene activation, we show that Paf1C regulates mitophagy independent of its positive regulatory role in other processes. More importantly, we also demonstrate the mitophagic role of PAF1C in mammals. Overall, we conclude that Paf1C maintains mitophagy at a low level through binding the promoter of the ATG32 gene in glucose-rich conditions. Dissociation of Paf1C from ATG32 leads to the increased expression of this gene, and mitophagy induction upon glucose starvation. Thus, we uncover a new role of Paf1C in modulating the mitophagy process at the transcriptional level.

Original languageEnglish
Pages (from-to)1366-1379
Number of pages14
JournalAutophagy
Volume16
Issue number8
Publication statusE-pub ahead of print - 19-Sep-2019

ID: 96977400