ArticleCell death and differentiation2023
Mitochondrial E3 ubiquitin ligase MARCHF5 controls BAK apoptotic activity independently of BH3-only proteins.
Article in Cell death and differentiation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- What does BCL-2 do? From new molecular insights to the clinical implications.Cell death and differentiation · 2026Review
- WWP2 underlies ROS-induced granulosa cell apoptosis by promoting ubiquitination of BAK in polycystic ovary syndrome.Cell death & disease · 2026Article
- A new era in cancer therapy: targeting the Proteasome-Bcl-2 axis.Journal of experimental & clinical cancer research : CR · 2025Review
- March5-mediated Trim28 degradation preserves islet β-cell function in mice.Nature communications · 2025Article
- Structural basis of BAK sequestration by MCL-1 in apoptosis.Molecular cell · 2025Article
- Inhibition of BAK-mediated apoptosis by the BH3-only protein BNIP5.Cell death and differentiation · 2025Article
- Deciphering MARCH5's impact on multiple myeloma: insights into autophagy regulation and AKT-FOXO3 signaling.Blood neoplasia · 2024Article
- Mitochondria and cell death.Nature cell biology · 2024Review
- Venetoclax Resistance in Acute Myeloid Leukemia.Cancers · 2024Review
- Apoptotic mitochondrial poration by a growing list of pore-forming BCL-2 family proteins.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- Regulation of apoptosis by ubiquitination in liver cancer.American journal of cancer research · 2023Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intrinsic apoptosis is principally governed by the BCL-2 family of proteins, but some non-BCL-2 proteins are also critical to control this process. To identify novel apoptosis regulators, we performed a genome-wide CRISPR-Cas9 library screen, and it identified the mitochondrial E3 ubiquitin ligase MARCHF5/MITOL/RNF153 as an important regulator of BAK apoptotic function. Deleting MARCHF5 in diverse cell lines dependent on BAK conferred profound resistance to BH3-mimetic drugs. The loss of MARCHF5 or its E3 ubiquitin ligase activity surprisingly drove BAK to adopt an activated conformation, with resistance to BH3-mimetics afforded by the formation of inhibitory complexes with pro-survival proteins MCL-1 and BCL-XL. Importantly, these changes to BAK conformation and pro-survival association occurred independently of BH3-only proteins and influence on pro-survival proteins. This study identifies a new mechanism by which MARCHF5 regulates apoptotic cell death by restraining BAK activating conformation change and provides new insight into how cancer cells respond to BH3-mimetic drugs. These data also highlight the emerging role of ubiquitin signalling in apoptosis that may be exploited therapeutically.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.