Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes

By R. Hamanaka, Navdeep S. Chandel. TIBS -Trends in Biochemical Sciences. Regular ed, 2010

974 citations recorded by the source corpus.

Reactive oxygen species (ROS) have historically been viewed as toxic metabolic byproducts and causal agents in a myriad of human pathologies. More recent work, however, indicates that ROS are critical intermediates of cellular signaling pathways. Although it is clear that dedicated cellular ROS producers such as NADPH oxidases participate in signaling, evidence suggests that mitochondrial production of ROS is also a tightly controlled process, and plays a role in the maintenance of cellular oxidative homeostasis and propagation of cellular signaling pathways. Production of ROS at mitochondria thus integrates cellular energy state, metabolite concentrations, and other upstream signaling events and has important implications in cellular stress signaling, maintenance of stem cell populations, cellular survival, and oncogenic transformation.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d15e7733a704b214863986af876214605f411a00

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. Navdeep S. Chandel
2. G. Shadel
3. S. Weinberg
4. S. Dikalov
5. S. Rhee
6. Y. Bae
7. Hyunjin Oh
8. Young Do Yoo

In Molecular Biology

1. Navdeep S. Chandel
2. S. Weinberg
3. G. Shadel
4. Lucas B. Sullivan
5. S. Dikalov
6. S. Rhee
7. Y. Bae
8. Hyunjin Oh

Citations in the corpus

• Mitochondria in innate immune responses (2011, background): “Mitochondrial regulation of apoptotic signalling has been appreciated for some time; however, more recent evidence suggests that mitochondria also participate in various additional signalling pathway”
• Mitochondrial electron transport chain: Oxidative phosphorylation, oxidant production, and methods of measurement (2020, background): “phosphorylation signaling [26,27], and cell growth and differentiation [28,29].”
• Reactive Oxygen Species Signaling and Oxidative Stress: Transcriptional Regulation and Evolution (2024, background): “…At physiological levels, ROS serve as crucial signaling molecules in a multitude of cellular functions, including but not limited to cell growth, proliferation, differentiation, apoptosis, immune response and stress adaptation [40]. enzymes, transcription factors and signaling cascades [4].”
• Mitochondria-Ros Crosstalk in the Control of Cell Death and Aging (2011, background): “Mitochondrially generated H2O2 can also act as a signaling molecule in the cytosol, affecting multiple networks that control, for example, cell cycle, stress response, energy metabolism, and redox balance [15–17].”
• MICU1 is an Essential Gatekeeper for MCU-Mediated Mitochondrial Ca2+ Uptake That Regulates Cell Survival (2012, positive): “Physiological mROS is implicated in many processes including gene expression, cell growth, proliferation and differentiation, whereas excessive mROS promotes cell death (Balaban et al., 2005; Hamanaka and Chandel, 2010).”
• Crosstalk between mitochondria and NADPH oxidases (2011, background): “Over the past several years, it has become clear that reactive oxygen species (ROS) play an important role in both physiological and pathological processes [1,2].”
• Mitochondrial complex III ROS regulate adipocyte differentiation (2011, positive): “Furthermore, our knowledge of ROS has become more complicated in the past decade, as the type of ROS and the compartmentalization of ROS are likely to regulate distinct biological outcomes (Hamanaka and Chandel, 2010).”
• Mitochondria: In Sickness and in Health (2012, background): “Multiple lines of evidence indicate that mitochondrial ROS also influence homeostatic signaling pathways to control cell proliferation and differentiation and to contribute to adaptive stress signaling pathways, such as hypoxia (Hamanaka and Chandel, 2010).”
• Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease (2015, neutral): “stimulate nuclear factor-κB (NF-κB) along with AP-1 to provide a second tier of defense against more severe oxidative stress [187, 188].”
• Mitochondrial ROS signaling in organismal homeostasis. (2015, background): “There is now extensive evidence from the study of model organisms supporting an active role for mtROS signaling in organismal physiology and adaptive responses (Hamanaka and Chandel, 2010; Ristow and Zarse, 2010; Yun and Finkel, 2014).”
• Mitochondrial dysfunction in pathophysiology of heart failure (2018, background): “In recent years, mtROS was also shown as a molecular mediator of hypoxia signaling, MAP kinase pathway, inflammation, and retrograde communication between mitochondria and nucleus (115, 116).”
• Regulation of reactive oxygen species generation in cell signaling (2011, methodology): “Mitochondrial superoxide is generated through the Q-cycle, as documented in recent papers (Andreyev et al., 2005; Hamanaka and Chandel, 2010; Turrens et al., 1985).”
• Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis (2014, positive): “An emerging function of mitochondria distinct from their ability to perform biosynthetic and bioenergetic reactions is the generation of H2O2, which promotes signaling in normal and cancer cells (Hamanaka and Chandel, 2010; Sena and Chandel, 2012).”