VDAC1 at the Intersection of Cell Metabolism, Apoptosis, and Diseases
Varda Shoshan-Barmatz1, Anna Shteinfer-Kuzmine1, Ankit Verma1
1Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Abstract:
The voltage-dependent anion channel 1 (VDAC1) protein, is an important regulator of mitochondrial function, and serves as a mitochondrial gatekeeper, with responsibility for cellular fate. In addition to control over energy sources and metabolism, the protein also regulates epigenomic elements and apoptosis via mediating the release of apoptotic proteins from the mitochondria. Apoptotic and pathological conditions, as well as certain viruses, induce cell death by inducing VDAC1 overexpression leading to oligomerization, and the formation of a large channel within the VDAC1 homo-oligomer. This then permits the release of pro-apoptotic proteins from the mitochondria and subsequent apoptosis. Mitochondrial DNA can also be released through this channel, which triggers type-Ι interferon responses. VDAC1 also participates in endoplasmic reticulum (ER)-mitochondria cross-talk, and in the regulation of autophagy, and inflammation. Its location in the outer mitochondrial membrane, makes VDAC1 ideally placed to interact with over 100 proteins, and to orchestrate the interaction of mitochondrial and cellular activities through a number of signaling pathways. Here, we provide insights into the multiple functions of VDAC1 and describe its involvement in several diseases, which demonstrate the potential of this protein as a druggable target in a wide variety of pathologies, including cancer.
Insights
The voltage-dependent anion channel 1 (VDAC1) protein regulates cell fate, apoptosis, and mitochondrial function. Its overexpression creates channels, releasing proteins and triggering cell death, highlighting its role in disease and as a drug target.
Area of Science:
- Mitochondrial Biology
- Cellular Signaling
- Molecular Medicine
Background:
- Voltage-dependent anion channel 1 (VDAC1) is a key regulator of mitochondrial function and cellular fate.
- VDAC1 controls energy metabolism, epigenomic elements, and apoptosis by mediating protein release from mitochondria.
Purpose of the Study:
- To provide insights into the diverse functions of VDAC1.
- To explore VDAC1's involvement in various diseases.
- To highlight VDAC1 as a potential therapeutic target.
Main Methods:
- Review of VDAC1's role in mitochondrial and cellular processes.
- Analysis of VDAC1's involvement in disease pathogenesis.
- Exploration of VDAC1's druggability.
Main Results:
- VDAC1 overexpression leads to channel formation, releasing pro-apoptotic proteins and inducing cell death.
- VDAC1 mediates mitochondrial DNA release, triggering inflammatory responses.
- VDAC1 is implicated in ER-mitochondria cross-talk, autophagy, and inflammation.
Conclusions:
- VDAC1 plays a critical role in regulating apoptosis, mitochondrial function, and cellular signaling.
- Dysregulation of VDAC1 is linked to various pathologies, including cancer.
- VDAC1 represents a promising druggable target for treating a wide range of diseases.
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