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Review

Valosin Containing Protein (VCP): A Multistep Regulator of Autophagy

by
Veronica Ferrari
1,
Riccardo Cristofani
1,
Barbara Tedesco
2,
Valeria Crippa
1,
Marta Chierichetti
1,
Elena Casarotto
1,
Marta Cozzi
1,
Francesco Mina
1,
Margherita Piccolella
1,
Mariarita Galbiati
1,
Paola Rusmini
1 and
Angelo Poletti
1,*
1
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy
2
Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS—Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(4), 1939; https://doi.org/10.3390/ijms23041939
Submission received: 21 December 2021 / Revised: 3 February 2022 / Accepted: 6 February 2022 / Published: 9 February 2022
(This article belongs to the Special Issue Molecular Genetics in Neurodegenerative Disorders)
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Abstract

Valosin containing protein (VCP) has emerged as a central protein in the regulation of the protein quality control (PQC) system. VCP mutations are causative of multisystem proteinopathies, which include neurodegenerative diseases (NDs), and share various signs of altered proteostasis, mainly associated with autophagy malfunctioning. Autophagy is a complex multistep degradative system essential for the maintenance of cell viability, especially in post-mitotic cells as neurons and differentiated skeletal muscle cells. Interestingly, many studies concerning NDs have focused on autophagy impairment as a pathological mechanism or autophagy activity boosting to rescue the pathological phenotype. The role of VCP in autophagy has been widely debated, but recent findings have defined new mechanisms associated with VCP activity in the regulation of autophagy, showing that VCP is involved in different steps of this pathway. Here we will discuss the multiple activity of VCP in the autophagic pathway underlying its leading role either in physiological or pathological conditions. A better understanding of VCP complexes and mechanisms in regulating autophagy could define the altered mechanisms by which VCP directly or indirectly causes or modulates different human diseases and revealing possible new therapeutic approaches for NDs.
Keywords: VCP; autophagy; lysophagy; TFEB; TFE3; NF-κB; neurodegenerative disease VCP; autophagy; lysophagy; TFEB; TFE3; NF-κB; neurodegenerative disease
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MDPI and ACS Style

Ferrari, V.; Cristofani, R.; Tedesco, B.; Crippa, V.; Chierichetti, M.; Casarotto, E.; Cozzi, M.; Mina, F.; Piccolella, M.; Galbiati, M.; et al. Valosin Containing Protein (VCP): A Multistep Regulator of Autophagy. Int. J. Mol. Sci. 2022, 23, 1939. https://doi.org/10.3390/ijms23041939

AMA Style

Ferrari V, Cristofani R, Tedesco B, Crippa V, Chierichetti M, Casarotto E, Cozzi M, Mina F, Piccolella M, Galbiati M, et al. Valosin Containing Protein (VCP): A Multistep Regulator of Autophagy. International Journal of Molecular Sciences. 2022; 23(4):1939. https://doi.org/10.3390/ijms23041939

Chicago/Turabian Style

Ferrari, Veronica, Riccardo Cristofani, Barbara Tedesco, Valeria Crippa, Marta Chierichetti, Elena Casarotto, Marta Cozzi, Francesco Mina, Margherita Piccolella, Mariarita Galbiati, and et al. 2022. "Valosin Containing Protein (VCP): A Multistep Regulator of Autophagy" International Journal of Molecular Sciences 23, no. 4: 1939. https://doi.org/10.3390/ijms23041939

APA Style

Ferrari, V., Cristofani, R., Tedesco, B., Crippa, V., Chierichetti, M., Casarotto, E., Cozzi, M., Mina, F., Piccolella, M., Galbiati, M., Rusmini, P., & Poletti, A. (2022). Valosin Containing Protein (VCP): A Multistep Regulator of Autophagy. International Journal of Molecular Sciences, 23(4), 1939. https://doi.org/10.3390/ijms23041939

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