Complex cellular responses to reactive oxygen species

Temple, Mark D.; Perrone, Gabriel G.; Dawes, Ian W.

doi:10.1016/j.tcb.2005.04.003

Cited by 354 publications

(306 citation statements)

References 80 publications

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“…Among the most conserved defense mechanisms against the oxidizing effects of H 2 O 2 are detoxifying enzymes, such as catalase, as well as aquaporins that control the influx of H 2 O 2 into the cell (3)(4)(5)(6)(7). These mechanisms are highly efficient and adaptable, and provide an explanation for the great variation in susceptibility to H 2 O 2 among cell types despite the generally low intracellular concentrations across bacteria, plants, and mammals (3,8,9). Indeed, it requires up to 10 mM exogenous H 2 O 2 to induce a measurable signaling response and more than 30 mM H 2 O 2 to induce necrotic blebbing in some mammalian cells, while plant tissues can contain up to 100 mM H 2 O 2 (10)(11)(12)(13).…”

mentioning

confidence: 99%

A respiratory chain controlled signal transduction cascade in the mitochondrial intermembrane space mediates hydrogen peroxide signaling

Patterson

Gerbeth

Thiru

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) govern cellular homeostasis by inducing signaling. H2O2 modulates the activity of phosphatases and many other signaling molecules through oxidation of critical cysteine residues, which led to the notion that initiation of ROS signaling is broad and nonspecific, and thus fundamentally distinct from other signaling pathways. Here, we report that H2O2 signaling bears hallmarks of a regular signal transduction cascade. It is controlled by hierarchical signaling events resulting in a focused response as the results place the mitochondrial respiratory chain upstream of tyrosine-protein kinase Lyn, Lyn upstream of tyrosine-protein kinase SYK (Syk), and Syk upstream of numerous targets involved in signaling, transcription, translation, metabolism, and cell cycle regulation. The active mediators of H2O2 signaling colocalize as H2O2 induces mitochondria-associated Lyn and Syk phosphorylation, and a pool of Lyn and Syk reside in the mitochondrial intermembrane space. Finally, the same intermediaries control the signaling response in tissues and species responsive to H2O2 as the respiratory chain, Lyn, and Syk were similarly required for H2O2 signaling in mouse B cells, fibroblasts, and chicken DT40 B cells. Consistent with a broad role, the Syk pathway is coexpressed across tissues, is of early metazoan origin, and displays evidence of evolutionary constraint in the human. These results suggest that H2O2 signaling is under control of a signal transduction pathway that links the respiratory chain to the mitochondrial intermembrane space-localized, ubiquitous, and ancient Syk pathway in hematopoietic and nonhematopoietic cells.

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mentioning

confidence: 99%

A respiratory chain controlled signal transduction cascade in the mitochondrial intermembrane space mediates hydrogen peroxide signaling

Patterson

Gerbeth

Thiru

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Although low levels of ROS are normally produced by the mitochondria and are usually detoxified quickly, an excessive accumulation of ROS -caused by UV or ionizing irradiation, chemical insult, or an aging cellmay trigger a diverse range of cellular responses, including cell growth, proliferation, or apoptosis. Complicating matters further, the effect of oxidizing agents seems to vary with the cell type tested, the dose and type of the oxidizing agent and the time of treatment (Boonstra and Post, 2004;Temple et al, 2005). Consistent with these observations, oxidizing agents have been shown to affect the mTOR pathway both positively and negatively.…”

Section: Rosmentioning

confidence: 65%

Upstream of the mammalian target of rapamycin: do all roads pass through mTOR?

2006

Oncogene

348

309

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The mammalian target of rapamycin (mTOR) is a serine/ threonine kinase that controls many aspects of cellular physiology, including transcription, translation, cell size, cytoskeletal organization and autophagy. Recent advances in the mTOR signaling field have found that mTOR exists in two heteromeric complexes, mTORC1 and mTORC2. The activity of mTORC1 is regulated by the integration of many signals, including growth factors, insulin, nutrients, energy availability and cellular stressors such as hypoxia, osmotic stress, reactive oxygen species and viral infection. In this review we highlight recent advances in the mTOR signaling field that relate to how the two mTOR complexes are regulated, and we discuss stress conditions linked to the mTOR signaling network that have not been extensively covered in other reviews. Given the diversity of signals that have been shown to impinge on mTOR, we also speculate on other signaltransduction pathways that may be linked to mTOR in the future.

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“…Involvement of MMP leading to cytochrome c release and activation of caspases in synergistic induction of apoptosis To explore the mechanisms by which mitochondrial uncouplers synergistically enhance imatinib-induced apoptosis of BCR/ABL-expressing cells, we examined the possible involvement of reactive oxygen species (ROS), which are produced mostly in mitochondria and are well-established regulators of apoptosis (Temple et al, 2005). Thus, we next analysed the effects of mitochondrial uncouplers and imatinib on levels of ROS in K562 cells using dihydroethidium (HE), a redox sensitive fluorescence probe for superoxide (Rothe and Valet, 1990).…”

Section: Resultsmentioning

confidence: 99%