Signal transduction to mitochondrial ATP synthase: Evidence that PDGF-dependent phosphorylation of the δ-subunit occurs in several cell lines, involves tyrosine, and is modulated by lysophosphatidic acid

Young Hee Ko, Weiying Pan, Chiyoko Inoue, Peter L. Pedersen

Research output: Contribution to journalArticle

Abstract

Although signal transduction mechanisms originating from receptors on the plasma membrane and targeted to metabolic and other enzymes/proteins localized in the cytoplasm or the nucleus have been extensively studied in animal cells, few such studies have focused on the mitochondrial energy producing machinery, i.e. the electron transport chain and ATP synthase complex (F0F1). Significantly, it was shown in an earlier collaborative study that platelet-derived growth factor (PDGF), which is linked in signal transduction pathways to tyrosine kinase-dependent phosphorylations, regulates the phosphorylation of the mitochondrial ATP synthase δ subunit in cortical neurons (Zhang et. al., 1995. J. Neurochem. 65, 2812-2815). This is a particularly intriguing finding in light of more recent reports demonstrating that ATP synthases are nanomotors with a central rotor, one component of which is the δ subunit. In this report, evidence is provided that the PDGF-dependent phosphorylation of the ATP synthase δ subunit is not confined to neuronal cells but can be demonstrated also in studies with PDGF-treated NIH3T3 and kidney cells. Evidence is provided also that phosphorylation of the ATP synthase δ subunit may involve its single tyrosine residue, and that this phosphorylation is modulated when the cell based assay includes lysophosphatidic acid (LPA), a phospholipid signaling molecules. Finally, results are presented of an analysis which revealed a number of potential tyrosine phosphorylation sites on three other subunits (α, β, and γ) of the F1 (catalytic) moiety of the mitochondrial ATP synthase, thus making this important complex a most attractive target for future signal transduction studies.

Original languageEnglish (US)
Pages (from-to)339-348
Number of pages10
JournalMitochondrion
Volume1
Issue number4
DOIs
StatePublished - Apr 15 2002

Keywords

  • ATP synthase
  • Lysophosphatidic acid
  • Mitochondria
  • Nanomotor
  • PDGF
  • Signal transduction
  • Tyrosine kinase
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cell Biology

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