Related Experiment Video
Updated: Jun 13, 2026
07:49
Transmitochondrial Cybrid Generation Using Cancer Cell Lines
Published on: March 17, 2023
A Cyclometalated Gold(III) Complex Targets Mitochondrial VDAC1 to Drive Immunometabolic Reprogramming in Cancer
Sean T Gilpatrick1, Jong Hyun Kim1, Sarayu Bhogoju2,3
1Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506, United States.
Journal of the American Chemical Society
|June 12, 2026
Summary
We discovered that a gold complex targets VDAC1, reprogramming cancer cell metabolism and inflammation. This mitochondrial targeting enhances immune cell anti-cancer activity, offering new therapeutic strategies.
Area of Science:
- Mitochondrial biology
- Cancer immunology
- Chemical biology
Background:
- Chemotherapy can alter immune and inflammatory pathways in cancer.
- The precise molecular links between drug action and immune changes are not well understood.
Purpose of the Study:
- To identify the molecular target of a gold(III) complex (AuPhos) and elucidate its role in cancer cell immunometabolic reprogramming.
- To establish a mechanistic link between drug engagement with a specific target and subsequent immune modulation.
Main Methods:
- Chemical proteomics
- Cellular thermal shift assays
- Intact and top-down mass spectrometry
- Analysis of cytokine and chemokine expression
- Assessment of peripheral blood mononuclear cell (PBMC) activation and cancer cell killing
Main Results:
- AuPhos directly and covalently binds to the mitochondrial voltage-dependent anion channel 1 (VDAC1) at cysteine 232.
- VDAC1 targeting by AuPhos disrupts mitochondrial metabolic homeostasis and induces pro-inflammatory signaling in cancer cells.
- AuPhos treatment enhances PBMC activation and boosts immune cell-mediated killing of cancer cells.
Conclusions:
- VDAC1 is a novel target for gold(III) complexes.
- AuPhos serves as a chemical probe and a prototype for metal-based agents that link mitochondrial targeting to immunometabolic reprogramming in cancer.
- These findings have implications for developing new cancer therapies targeting mitochondrial and immune pathways.
Related Concept Videos
01:46Electron Transport Chain: Complex I and II
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
02:57Targeted Cancer Therapies
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
There are several types of targeted therapies against specific...
02:57Targeted Cancer Therapies
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
There are several types of targeted therapies against specific...
03:03mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
03:03mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
01:27Tumor Immunotherapy
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.