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Mitochondrial quality control systems sustain brain mitochondrial bioenergetics in early stages of type 2 diabetes

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Abstract

Mitochondria have a crucial role in the supply of energy to the brain. Mitochondrial alterations can lead to detrimental consequences on the function of brain cells and are thought to have a pivotal role in the pathogenesis of several neurologic disorders. This study was aimed to evaluate mitochondrial function, fusion–fission and biogenesis and autophagy in brain cortex of 6-month-old Goto–Kakizaki (GK) rats, an animal model of nonobese type 2 diabetes (T2D). No statistically significant alterations were observed in mitochondrial respiratory chain and oxidative phosphorylation system. A significant decrease in the protein levels of OPA1, a protein that facilitates mitochondrial fusion, was observed in brain cortex of GK rats. Furthermore, a significant decrease in the protein levels of LC3-II and a significant increase in protein levels of mTOR phosphorylated at serine residue 2448 were observed in GK rats suggesting a suppression of autophagy in diabetic brain cortex. No significant alterations were observed in the parameters related to mitochondrial biogenesis. Altogether, these results demonstrate that during the early stages of T2D, brain mitochondrial function is maintained in part due to a delicate balance between mitochondrial fusion–fission and biogenesis and autophagy. However, future studies are warranted to evaluate the role of mitochondrial quality control pathways in late stages of T2D.

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Acknowledgments

Renato X. Santos has a PhD fellowship from the Fundação para a Ciência e a Tecnologia (SFRH/BD/43972/2008).

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Authors and Affiliations

  1. Department of Life Sciences – Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal

    R. X. Santos, S. Cardoso, C. Carvalho & M. S. Santos

  2. CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

    R. X. Santos, S. C. Correia, S. Cardoso, C. Carvalho, M. S. Santos & P. I. Moreira

  3. Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal

    S. C. Correia

  4. CICS – UBI – Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal

    M. G. Alves & P. F. Oliveira

  5. Faculty of Medicine, IBILI - Institute for Biomedical Imaging and Life Sciences, University of Coimbra, Coimbra, Portugal

    R. Seiça

  6. Laboratory of Physiology – Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    R. Seiça & P. I. Moreira

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  1. R. X. Santos
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Correspondence to P. I. Moreira.

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Santos, R.X., Correia, S.C., Alves, M.G. et al. Mitochondrial quality control systems sustain brain mitochondrial bioenergetics in early stages of type 2 diabetes. Mol Cell Biochem 394, 13–22 (2014). https://doi.org/10.1007/s11010-014-2076-5

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