Cited by 225Cell death mechanisms and regulationLiver Disease Diagnosis and TreatmentLiver physiology and pathology

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Lytic cell death in metabolic liver disease

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Gautheron, Jérémie, Gores, Gregory J., Rodrigues, Cecília M.P.·2020·Journal of Hepatology

DOI 10.1016/j.jhep.2020.04.001PMC PMC7371520

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Abstract

Regulated cell death is intrinsically associated with inflammatory liver disease and is pivotal in governing outcomes of metabolic liver disease. Different types of cell death may coexist as metabolic liver disease progresses to inflammation, fibrosis, and ultimately cirrhosis. In addition to apoptosis, lytic forms of hepatocellular death, such as necroptosis, pyroptosis and ferroptosis elicit strong inflammatory responses due to cell membrane permeabilisation and release of cellular components, contributing to the recruitment of immune cells and activation of hepatic stellate cells. The control of liver cell death is of fundamental importance and presents novel opportunities for potential therapeutic intervention. This review summarises the underlying mechanism of distinct lytic cell death modes and their commonalities, discusses their relevance to metabolic liver diseases of different aetiologies, and acknowledges the limitations of current knowledge in the field. We focus on the role of hepatocyte necroptosis, pyroptosis and ferroptosis in non-alcoholic fatty liver disease, alcohol-associated liver disease and other metabolic liver disorders, as well as potential therapeutic implications.

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1 retracted

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Background

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Sorted by citations

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Background
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Background
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Background
Manipulating PP2Acα-ASK-JNK signaling to favor apoptotic over necroptotic hepatocyte fate reduces the extent of necrosis and fibrosis upon acute liver injury
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Self-citation
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“Consistent with prior studies showing that ferroptosis inhibition alleviates liver injury [10, 36], our data suggest that IP6K3 may act as a pro-ferroptotic regulator in the MASLD context.”
NAD+ depletion links metabolic stress to drive innate immune priming and selectively control PANoptosis
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“9 Apoptosis maintains the integrity of the plasma membrane, with apoptotic effectors contributing to immune silencing.”
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Jamali, H., Pezeshki, Z., Choopani, S., Pourvali, B., Khaleghi, M. M., Hashemnia, M., Mehranfard, N., & Ghasemi, M. (2025) · Biological Trace Element Research · doi:10.1007/s12011-025-04722-x · Cited by 1
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Self-citation

Authors: Gautheron, J., Gores, G. J., & Rodrigues, C. M. P.
Affiliations: Inserm (FR)
Mayo Clinic (US)
University of Lisbon (PT)
Corresponding author: Rodrigues, Cecília M.P.
ORCID: Gautheron, Jérémie
Gores, Gregory J.
Rodrigues, Cecília M.P.
Venue: Journal of Hepatology
Publisher: Elsevier BV
Published: 2020-08
Volume: 73
Issue: 2
Pages: 394-408
ISSN: 0168-8278 (ISSN-L)
DOI: 10.1016/j.jhep.2020.04.001
PMC: PMC7371520
OpenAlex: W3016394009
Cited by: 225
References: 148
Citations by year: 2026: 31 · 2025: 32 · 2024: 49 · 2023: 40 · 2022: 42 · 2021: 23 · 2020: 8
FWCI: 2.70
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Journal of Hepatology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
HAL (submittedVersion, other-oa)
Funders: Fondation pour la Recherche Médicale
Fundação para a Ciência e a Tecnologia
National Institutes of Health
H2020 Marie Skłodowska-Curie Actions
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords: lytic cell death, metabolic liver disease, pyroptosis, ferroptosis, apoptosis, liver inflammation, liver fibrosis, liver cirrhosis, hepatic stellate cells, non-alcoholic fatty liver disease, alcoholic liver disease, therapeutic target
MeSH terms: Pyroptosis, Necroptosis, Ferroptosis, Regulated Cell Death, Humans, Liver Diseases, Drug Discovery

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Lytic cell death in metabolic liver disease

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