The VDAC1 N-terminus is essential both for apoptosis and the protective effect of anti-apoptotic proteins
Abstract
The release of mitochondrial-intermembrane-space pro-apoptotic proteins, such as cytochrome c, is a key step in initiating apoptosis. Our study addresses two major questions in apoptosis: how are mitochondrial pro-apoptotic proteins released and how is this process regulated? Accumulating evidence indicates that the voltage-dependent anion channel (VDAC) plays a central role in mitochondria-mediated apoptosis. Here, we demonstrate that the N-terminal domain of VDAC1 controls the release of cytochrome c, apoptosis and the regulation of apoptosis by anti-apoptotic proteins such as hexokinase and Bcl2. Cells expressing N-terminal truncated VDAC1 do not release cytochrome c and are resistant to apoptosis, induced by various stimuli. Employing a variety of experimental approaches, we show that hexokinase and Bcl2 confer protection against apoptosis through interaction with the VDAC1 N-terminal region. We also demonstrate that apoptosis induction is associated with VDAC oligomerization. These results show VDAC1 to be a component of the apoptosis machinery and offer new insight into the mechanism of cytochrome c release and how anti-apoptotic proteins regulate apoptosis and promote tumor cell survival.
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The N-terminal domain of VDAC1 interacts with several Bcl-2 family proteins that regulate apoptosis and is involved in gating the channel.
“The N-terminal domain of VDAC1 interacts with several Bcl-2 family proteins that regulate apoptosis and is involved in gating the channel [96,97,98,99,100,101].”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [99]
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Self-citation
- Authors
- Abu-Hamad, S., Arbel, N., Calo, D., Arzoine, L., Israelson, A., Keinan, N., Ben-Romano, R., Friedman, O., & Shoshan-Barmatz, V.
- Affiliations
- Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel
- Ben-Gurion University of the Negev (IL)
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2009-06-01
- Volume
- 122
- Issue
- 11
- Pages
- 1906-1916
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W1989593508
- Cited by
- 226
- References
- 62
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 10 · 2023: 10 · 2022: 6 · 2021: 20 · 2020: 9 · 2019: 9 · 2018: 17 · 2017: 19 · 2016: 20 · 2015: 12 · 2014: 17 · 2013: 9 · 2012: 16
- FWCI
- 7.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Keywords
- VDAC1, voltage-dependent anion channel, N-terminal domain, apoptosis, cytochrome c release, mitochondrial intermembrane space, hexokinase, Bcl-2, anti-apoptotic proteins, tumor cell survival, mitochondrial permeability transition
- MeSH terms
- Animals, Cell Line, Hexokinase, Humans, Mitochondria, Models, Molecular, Mutation, Peptides, Recombinant Fusion Proteins, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Cytochromes c, Voltage-Dependent Anion Channel 1, Apoptosis Regulatory Proteins, Mice
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