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Manganese superoxide dismutase (SOD2): is there a center in the universe of mitochondrial redox signaling?

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Abstract

It is becoming increasingly clear that mitochondria drive cellular functions and in vivo phenotypes by directing the production rate and abundance of metabolites that are proposed to function as signaling molecules (Chandel 2015; Selak et al. 2005; Etchegaray and Mostoslavsky 2016). Many of these metabolites are intermediates that make up cellular metabolism, part of which occur in mitochondria (i.e. the TCA and urea cycles), while others are produced “on demand” mainly in response to alterations in the microenvironment in order to participate in the activation of acute adaptive responses (Mills et al. 2016; Go et al. 2010). Reactive oxygen species (ROS) are well suited for the purpose of executing rapid and transient signaling due to their short lived nature (Bae et al. 2011). Hydrogen peroxide (H2O2), in particular, possesses important characteristics including diffusibility and faster reactivity with specific residues such as methionine, cysteine and selenocysteine (Bonini et al. 2014). Therefore, it is reasonable to propose that H2O2 functions as a relatively specific redox signaling molecule. Even though it is now established that mtH2O2 is indispensable, at least for hypoxic adaptation and energetic and/or metabolic homeostasis (Hamanaka et al. 2016; Guzy et al. 2005), the question of how H2O2 is produced and regulated in the mitochondria is only partially answered. In this review, some roles of this indispensable signaling molecule in driving cellular metabolism will be discussed. In addition, we will discuss how H2O2 formation in mitochondria depends on and is controlled by MnSOD. Finally, we will conclude this manuscript by highlighting why a better understanding of redox hubs in the mitochondria will likely lead to new and improved therapeutics of a number of diseases, including cancer.

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Financial support

D. Gius is supported by 2R01CA152601-A1, 1R01CA152799-01A1, 1R01CA168292- 01A1, 1R01CA214025-01, the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust, Zell Family Foundation, and the Avon Foundation for Breast Cancer Research. Y. Zhu is supported by a Robert H. Lurie Comprehensive Cancer Center Translation Bridge Fellowship Award.

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Authors and Affiliations

  1. Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Room 3-250, Lurie Research Building, 303 East Superior, Chicago, IL, 60611, USA

    Xianghui Zou, Joseph Gerald O’Brien, David R. Gius & Yueming Zhu

  2. Department of Pharmacology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Xianghui Zou, Joseph Gerald O’Brien, David R. Gius & Yueming Zhu

  3. Driskill Graduate Program in Life Science, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Xianghui Zou

  4. Programa de Biociencias Aplicadas a Farmacia (PBF), Universidade Estadual de Maringa, Maringa, PR, Brazil

    Bianca A. Ratti & Sueli O. Lautenschlager

  5. Departments of Medicine and Pathology, University of Illinois College of Medicine in Chicago, Chicago, IL, USA

    Bianca A. Ratti & Marcelo G. Bonini

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  1. Xianghui Zou
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Correspondence to Yueming Zhu.

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Zou, X., Ratti, B.A., O’Brien, J.G. et al. Manganese superoxide dismutase (SOD2): is there a center in the universe of mitochondrial redox signaling?. J Bioenerg Biomembr 49, 325–333 (2017). https://doi.org/10.1007/s10863-017-9718-8

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