{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:57:13Z","timestamp":1760151433825,"version":"build-2065373602"},"reference-count":58,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T00:00:00Z","timestamp":1647993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms23073498","type":"journal-article","created":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T12:20:25Z","timestamp":1648038025000},"page":"3498","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Autophagy Alteration in ApoA-I Related Systemic Amyloidosis"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9927-9413","authenticated-orcid":false,"given":"Rita Del","family":"Del Giudice","sequence":"first","affiliation":[{"name":"Department of Chemical Sciences, University of Napoli Federico II, Complesso Universitario Monte Sant\u2019Angelo, 80126 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Imbimbo","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Napoli Federico II, Complesso Universitario Monte Sant\u2019Angelo, 80126 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Pietrocola","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Nutrition, Karolinska Institute, 14157 Huddinge, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Martins","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, INSERM U1138, Universit\u00e9 Paris Cit\u00e9, Sorbonne Universit\u00e9, 75006 Paris, France"},{"name":"Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, 94805 Villejuif, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6109-2768","authenticated-orcid":false,"given":"Fatima Domenica Elisa","family":"De Palma","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, INSERM U1138, Universit\u00e9 Paris Cit\u00e9, Sorbonne Universit\u00e9, 75006 Paris, France"},{"name":"CEINGE-Biotecnologie Avanzate s.c.a.r.l., 80145 Napoli, Italy"},{"name":"Department of Molecular Medicine and Medical Biotechnologies, University of Napoli Federico II, 80131 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Manuel","family":"Bravo-San Pedro","sequence":"additional","affiliation":[{"name":"Departamento de Fisiologia, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9334-4405","authenticated-orcid":false,"given":"Guido","family":"Kroemer","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, INSERM U1138, Universit\u00e9 Paris Cit\u00e9, Sorbonne Universit\u00e9, 75006 Paris, France"},{"name":"Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, 94805 Villejuif, France"},{"name":"Institut Universitaire de France, 75005 Paris, France"},{"name":"P\u00f4le de Biologie, H\u00f4pital Europ\u00e9en Georges Pompidou, Ap-hp, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Chiara","family":"Maiuri","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, INSERM U1138, Universit\u00e9 Paris Cit\u00e9, Sorbonne Universit\u00e9, 75006 Paris, France"},{"name":"Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, 94805 Villejuif, France"},{"name":"Pharmacy Department, University of Napoli Federico II, 80131 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1136-0576","authenticated-orcid":false,"given":"Daria Maria","family":"Monti","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Napoli Federico II, Complesso Universitario Monte Sant\u2019Angelo, 80126 Napoli, Italy"},{"name":"Istituto Nazionale di Biostrutture e Biosistemi (INBB), 00136 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1146\/annurev.biochem.75.101304.123901","article-title":"Protein misfolding, functional amyloid, and human disease","volume":"75","author":"Chiti","year":"2006","journal-title":"Annu. 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