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Review

Regulation of Autophagy by Nuclear GAPDH and Its Aggregates in Cancer and Neurodegenerative Disorders

1
Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biochemistry, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy
2
Research Center LURM (Interdepartmental Laboratory of Medical Research), University of Verona, 37134 Verona, Italy
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(9), 2062; https://doi.org/10.3390/ijms20092062
Received: 28 March 2019 / Revised: 21 April 2019 / Accepted: 23 April 2019 / Published: 26 April 2019
Several studies indicate that the cytosolic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has pleiotropic functions independent of its canonical role in glycolysis. The GAPDH functional diversity is mainly due to post-translational modifications in different amino acid residues or due to protein–protein interactions altering its localization from cytosol to nucleus, mitochondria or extracellular microenvironment. Non-glycolytic functions of GAPDH include the regulation of cell death, autophagy, DNA repair and RNA export, and they are observed in physiological and pathological conditions as cancer and neurodegenerative disorders. In disease, the knowledge of the mechanisms regarding GAPDH-mediated cell death is becoming fundamental for the identification of novel therapies. Here, we elucidate the correlation between autophagy and GAPDH in cancer, describing the molecular mechanisms involved and its impact in cancer development. Since autophagy is a degradative pathway associated with the regulation of cell death, we discuss recent evidence supporting GAPDH as a therapeutic target for autophagy regulation in cancer therapy. Furthermore, we summarize the molecular mechanisms and the cellular effects of GAPDH aggregates, which are correlated with mitochondrial malfunctions and can be considered a potential therapeutic target for various diseases, including cancer and neurodegenerative disorders. View Full-Text
Keywords: GAPDH; autophagy; cancer; aggregates; cell death GAPDH; autophagy; cancer; aggregates; cell death
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MDPI and ACS Style

Butera, G.; Mullappilly, N.; Masetto, F.; Palmieri, M.; Scupoli, M.T.; Pacchiana, R.; Donadelli, M. Regulation of Autophagy by Nuclear GAPDH and Its Aggregates in Cancer and Neurodegenerative Disorders. Int. J. Mol. Sci. 2019, 20, 2062. https://doi.org/10.3390/ijms20092062

AMA Style

Butera G, Mullappilly N, Masetto F, Palmieri M, Scupoli MT, Pacchiana R, Donadelli M. Regulation of Autophagy by Nuclear GAPDH and Its Aggregates in Cancer and Neurodegenerative Disorders. International Journal of Molecular Sciences. 2019; 20(9):2062. https://doi.org/10.3390/ijms20092062

Chicago/Turabian Style

Butera, Giovanna, Nidula Mullappilly, Francesca Masetto, Marta Palmieri, Maria T. Scupoli, Raffaella Pacchiana, and Massimo Donadelli. 2019. "Regulation of Autophagy by Nuclear GAPDH and Its Aggregates in Cancer and Neurodegenerative Disorders" International Journal of Molecular Sciences 20, no. 9: 2062. https://doi.org/10.3390/ijms20092062

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