Isoform-specific localization of A-RAF in mitochondria

Anton Yuryev, Makoto Ono, Stephen A. Goff, Frank Macaluso, Lawrence P. Wennogle

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


RAF kinase is a family of isoforms including A-RAF, B-RAF, and C-RAF. Despite the important role of RAF in cell growth and proliferation, little evidence exists for isoform-specific function of RAF family members. Using western analysis and immunogold labeling, A-RAF was selectively localized in highly purified rat liver mitochondria. Two novel human proteins, which interact specifically with A-RAF, were identified, and the full-length sequences are reported. These proteins, referred to as hTOM and hTIM, are similar to components of mitochondrial outer and inner membrane protein- import receptors from lower organisms, implicating their involvement in the mitochondrial transport of A-RAF, hTOM contains multiple tetratricopeptide repeat (TPR) domains, which function in protein-protein interactions. TPR domains are frequently present in proteins involved in cellular transport systems. In contrast, protein 14-3-3, an abundant cytosolic protein that participates in many facets of signal transduction, was found to interact with C-RAF but not with A-RAF N-terminal domain. This information is discussed in view of the important role of mitochondria in cellular functions involving energy balance, proliferation, and apoptosis and the potential role of A-RAF in regulating these systems.

Original languageEnglish (US)
Pages (from-to)4870-4878
Number of pages9
JournalMolecular and cellular biology
Issue number13
StatePublished - Jul 2000

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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