Control of mitochondrial structure and function by the Yorkie/YAP oncogenic pathway

Raghavendra Nagaraj, Shubha Gururaja-Rao, Kevin T. Jones, Matthew Slattery, Nicolas Negre, Daniel Braas, Heather Christofk, Kevin P. White, Richard Mann, Utpal Banerjee

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

Mitochondrial structure and function are highly dynamic, but the potential roles for cell signaling pathways in influencing these properties are not fully understood. Reduced mitochondrial function has been shown to cause cell cycle arrest, and a direct role of signaling pathways in controlling mitochondrial function during development and disease is an active area of investigation. Here, we show that the conserved Yorkie/YAP signaling pathway implicated in the control of organ size also functions in the regulation of mitochondria in Drosophila as well as human cells. In Drosophila, activation of Yorkie causes direct transcriptional up-regulation of genes that regulate mitochondrial fusion, such as opa1-like (opa1) and mitochondria assembly regulatory factor (Marf), and results in fused mitochondria with dramatic reduction in reactive oxygen species (ROS) levels. When mitochondrial fusion is genetically attenuated, the Yorkie-induced cell proliferation and tissue overgrowth are significantly suppressed. The function of Yorkie is conserved across evolution, as activation of YAP2 in human cell lines causes increased mitochondrial fusion. Thus, mitochondrial fusion is an essential and direct target of the Yorkie/YAP pathway in the regulation of organ size control during development and could play a similar role in the genesis of cancer.

Original languageEnglish (US)
Pages (from-to)2027-2037
Number of pages11
JournalGenes and Development
Volume26
Issue number18
DOIs
StatePublished - Sep 15 2012
Externally publishedYes

Keywords

  • Hippo pathway
  • Marf
  • Mitochondrial fusion
  • Opa
  • ROS
  • Yap
  • Yorkie

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