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Sci. STKE, 17 August 2004
Vol. 2004, Issue 246, p. tw295
[DOI: 10.1126/stke.2462004tw295]


REDOX REGULATION Receptor Regulation Through Mitochondria

Reactive oxygen species mediate effects of oxidative stress but also appear to function as signaling molecules. H2O2, for example, causes activation of the epidermal growth factor receptor (EGFR) and other receptors and activation of the c-Jun N-terminal protein kinase (Jnk) and the kinase Akt, but exactly how this occurs remains an open question. Chen et al. report experiments consistent with a critical role of the mitochondria in producing the signaling effects of H2O2. Pharmacological inhibition of mitochondrial respiration at complex I, complex III, or complex IV reduced the effects of H2O2 on tyrosine phosphorylation of the EFGR and activation of Jnk and Akt. Antioxidants targeted to the mitochondria also reduced H2O2-dependent activation of the EGFR, Jnk, and Akt, whereas an antioxidant that distributes evenly throughout the cell was ineffective. Inhibition of protein tyrosine phosphatase activity is one previously proposed target of H2O2. However, effects on PTP activity were not affected by the inhibitors of respiration nor by the mitochondrially targeted antioxidant. The authors propose that effects of H2O2 on the EGFR and other receptors result from events early in the signaling pathway occurring in the mitochondria.

K. Chen, S. R. Thomas, A. Albano, M. P. Murphy, J. F. Keaney Jr., Mitochondrial function is required for hydrogen peroxide—induced growth factor receptor transactivation and downstream signaling. J. Biol. Chem. 279, 35079-35086 (2004). [Abstract] [Full Text]

Citation: Receptor Regulation Through Mitochondria. Sci. STKE 2004, tw295 (2004).

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