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Article

Autophagy Alteration in ApoA-I Related Systemic Amyloidosis

by
Rita Del Giudice
1,†,
Paola Imbimbo
1,†,
Federico Pietrocola
2,
Isabelle Martins
3,4,
Fatima Domenica Elisa De Palma
3,5,6,
José Manuel Bravo-San Pedro
7,
Guido Kroemer
3,4,8,9,
Maria Chiara Maiuri
3,4,10 and
Daria Maria Monti
1,11,*
1
Department of Chemical Sciences, University of Napoli Federico II, Complesso Universitario Monte Sant’Angelo, 80126 Napoli, Italy
2
Department of Biosciences and Nutrition, Karolinska Institute, 14157 Huddinge, Sweden
3
Centre de Recherche des Cordeliers, INSERM U1138, Université Paris Cité, Sorbonne Université, 75006 Paris, France
4
Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, 94805 Villejuif, France
5
CEINGE-Biotecnologie Avanzate s.c.a.r.l., 80145 Napoli, Italy
6
Department of Molecular Medicine and Medical Biotechnologies, University of Napoli Federico II, 80131 Napoli, Italy
7
Departamento de Fisiologia, Universidad Complutense de Madrid, 28040 Madrid, Spain
8
Institut Universitaire de France, 75005 Paris, France
9
Pôle de Biologie, Hôpital Européen Georges Pompidou, Ap-hp, 75015 Paris, France
10
Pharmacy Department, University of Napoli Federico II, 80131 Napoli, Italy
11
Istituto Nazionale di Biostrutture e Biosistemi (INBB), 00136 Rome, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2022, 23(7), 3498; https://doi.org/10.3390/ijms23073498
Submission received: 8 February 2022 / Revised: 16 March 2022 / Accepted: 18 March 2022 / Published: 23 March 2022
(This article belongs to the Special Issue Molecular Research on Amyloidosis)

Abstract

Amyloidoses are characterized by the accumulation and aggregation of misfolded proteins into fibrils in different organs, leading to cell death and consequent organ dysfunction. The specific substitution of Leu 75 for Pro in Apolipoprotein A-I protein sequence (ApoA-I; L75P-ApoA-I) results in late onset amyloidosis, where deposition of extracellular protein aggregates damages the normal functions of the liver. In this work, we describe that the autophagic process is inhibited in the presence of the L75P-ApoA-I amyloidogenic variant in stably transfected human hepatocyte carcinoma cells. The L75P-ApoA-I amyloidogenic variant alters the redox status of the cells, resulting into excessive mitochondrial stress and consequent cell death. Moreover, L75P-ApoA-I induces an impairment of the autophagic flux. Pharmacological induction of autophagy or transfection-enforced overexpression of the pro-autophagic transcription factor EB (TFEB) restores proficient proteostasis and reduces oxidative stress in these experimental settings, suggesting that pharmacological stimulation of autophagy could be a promising target to alleviate ApoA-I amyloidosis.
Keywords: amyloidosis; autophagy; apoptosis; apolipoprotein A-I amyloidosis; autophagy; apoptosis; apolipoprotein A-I
Graphical Abstract

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MDPI and ACS Style

Del Giudice, R.; Imbimbo, P.; Pietrocola, F.; Martins, I.; De Palma, F.D.E.; Bravo-San Pedro, J.M.; Kroemer, G.; Maiuri, M.C.; Monti, D.M. Autophagy Alteration in ApoA-I Related Systemic Amyloidosis. Int. J. Mol. Sci. 2022, 23, 3498. https://doi.org/10.3390/ijms23073498

AMA Style

Del Giudice R, Imbimbo P, Pietrocola F, Martins I, De Palma FDE, Bravo-San Pedro JM, Kroemer G, Maiuri MC, Monti DM. Autophagy Alteration in ApoA-I Related Systemic Amyloidosis. International Journal of Molecular Sciences. 2022; 23(7):3498. https://doi.org/10.3390/ijms23073498

Chicago/Turabian Style

Del Giudice, Rita, Paola Imbimbo, Federico Pietrocola, Isabelle Martins, Fatima Domenica Elisa De Palma, José Manuel Bravo-San Pedro, Guido Kroemer, Maria Chiara Maiuri, and Daria Maria Monti. 2022. "Autophagy Alteration in ApoA-I Related Systemic Amyloidosis" International Journal of Molecular Sciences 23, no. 7: 3498. https://doi.org/10.3390/ijms23073498

APA Style

Del Giudice, R., Imbimbo, P., Pietrocola, F., Martins, I., De Palma, F. D. E., Bravo-San Pedro, J. M., Kroemer, G., Maiuri, M. C., & Monti, D. M. (2022). Autophagy Alteration in ApoA-I Related Systemic Amyloidosis. International Journal of Molecular Sciences, 23(7), 3498. https://doi.org/10.3390/ijms23073498

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