Unlocking nervous system function through ROS and mitochondrial signaling – a FEBS Letters Special Issue

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Introducing a FEBS Letters Special Issue on ‘ROS and mitochondria in nervous system function and disease’:

ROS (reactive oxygen species) have long been known to be damaging by-products of metabolism, but the concept that ROS-mediated modification of proteins plays a signalling role in neurons is rapidly gaining ground [1]. Mitochondria generate ATP, but are also important organelles in neuronal signal transduction and are the main source of ROS [2-4]. Neurons are highly polarised cells that require mitochondria at pre-synapses to provide a local ATP supply to power neurotransmitter release and synaptic vesicle recycling [5]. Higher mitochondrial activity implies an increased likelihood of ROS generation in neurons. Furthermore, neurons are post-mitotic and long living and so particularly sensitive to oxidative stress. Therefore, neuronal cells require more efficient mechanisms to protect against oxidative stress. Conversely, neurons also have the opportunity to exploit ROS as a homeostatic signalling mechanism. These interconnected roles mean that ROS and mitochondria are vitally important, not only in nervous system development and function, but also in neurological disease.

In this Special Issue, edited by Joseph Bateman and Wilhelm Just, experts in the field discuss in great depth the current understanding of the roles of ROS and mitochondria in normal neural physiology and in a variety of pathological contexts.

ROS can directly affect signalling pathways through modification of the redox state of key signalling proteins. The important roles of mitochondria and ROS in signalling in the nervous system are one focus of this Special Issue [6,7].

A number of reviews highlight the role of mitochondria in ROS production and redox homeostasis in the brain, as well as the involvement of mitochondrial ROS in the mechanism of neuronal loss in neurodegenerative disease and ageing [8-12].

Inefficient mitochondrial protein import can also affect the cytosolic proteome and proteostatic signalling. Coyne and Chen review this topic and discuss the potential contribution of this mechanism to protein aggregation-associated neurodegenerative diseases [13].

Mortiboys and colleagues review the current state of translational approaches to restoring mitochondrial function in Parkinson’s disease [14]. In addition, Kang et al. discuss the current understanding of the role of TFAM, a mitochondrial DNA binding protein and transcription factor, in common neurodegenerative diseases [15]. Finally, a review by Thornton and colleagues discusses mitochondrial dynamics, mitophagy and biogenesis in neonatal hypoxic-ischaemic brain injury [16].

Overall the contributions in this Special Issue illustrate the inter-linked roles of ROS and mitochondria in neurons during normal physiology, and their contribution to a variety of neurodegenerative diseases. We thank the authors for their thought-provoking contributions and we hope that our readers will find them inspiring.


[1]        Reczek, C.R. and Chandel, N.S. (2015). ROS-dependent signal transduction. Curr Opin Cell Biol 33, 8-13.

[2]        Cagin, U., Duncan, O.F., Gatt, A.P., Dionne, M.S., Sweeney, S.T. and Bateman, J.M. (2015). Mitochondrial retrograde signaling regulates neuronal function. Proc Natl Acad Sci U S A 112,  E6000-9.

[3]        Chandel, N.S. (2014). Mitochondria as signaling organelles. BMC Biol 12, 34

[4]        Duncan, O.F. and Bateman, J.M. (2016). Mitochondrial retrograde signaling in the Drosophila nervous system and beyond. Fly (Austin) 10, 1-6.

[5]        Devine, M.J. and Kittler, J.T. (2018). Mitochondria at the neuronal presynapse in health and disease. Nat Rev Neurosci 19,  63-80.

[6]        Hunt, R.J. and Bateman, J.M. (2017). Mitochondrial retrograde signaling in the nervous system. FEBS Lett, 10.1002/1873-3468.12890

[7]        Oswald, M.C.W., Garnham, N., Sweeney, S.T. and Landgraf, M. (2018). Regulation of neuronal development and function by ROS. FEBS Lett, 10.1002/1873-3468.12972

[8]        Angelova, P.R. and Abramov, A.Y. (2018). Role of mitochondrial ROS in the brain: from physiology to neurodegeneration. FEBS Lett, 10.1002/1873-3468.12964

[9]        Boczonadi, V., Jennings, M.J. and Horvath, R. (2017). The role of tRNA synthetases in neurological and neuromuscular disorders. FEBS Lett, 10.1002/1873-3468.12962

[10]      Lupoli, F., Vannocci, T., Longo, G., Niccolai, N. and Pastore, A. (2017). The role of oxidative stress in Friedreich's ataxia. FEBS Lett, 10.1002/1873-3468.12928

[11]      Nissanka, N. and Moraes, C.T. (2017). Mitochondrial DNA damage and reactive oxygen species in neurodegenerative disease. FEBS Lett, 10.1002/1873-3468.12956

[12]      Stefanatos, R. and Sanz, A. (2017). The role of mitochondrial ROS in the aging brain. FEBS Lett, 10.1002/1873-3468.12902

[13]      Coyne, L.P. and Chen, X.J. (2017). mPOS is a novel mitochondrial trigger of cell death - implications for neurodegeneration. FEBS Lett, 10.1002/1873-3468.12894

[14]      Mortiboys, H., Macdonald, R., Payne, T., Sassani, M., Jenkins, T. and Bandmann, O. (2017). Translational approaches to restoring mitochondrial function in Parkinson's disease. FEBS Lett, 10.1002/1873-3468.12920

[15]      Kang, I., Chu, C.T. and Kaufman, B.A. (2018). The mitochondrial transcription factor TFAM in neurodegeneration: Emerging evidence and mechanisms. FEBS Lett, 10.1002/1873-3468.12989

[16]      Thornton, C., Jones, A., Nair, S., Aabdien, A., Mallard, C. and Hagberg, H. (2017). Mitochondrial dynamics, mitophagy and biogenesis in neonatal hypoxic-ischaemic brain injury. FEBS Lett, 10.1002/1873-3468.12943

Modified from Bateman, J.M. (2018) Special Issue on ‘ROS and mitochondria in nervous system function and disease’. FEBS Lett, 592: 661–662. doi:10.1002/1873-3468.13008





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