Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study points to new drug target in fight against cancer

19.09.2019

Research shows how a cancer-linked protein blocks key mitochondrial gateway

Researchers have identified a potential new drug target in the fight against cancer.


When oxidized, the protein mitoNEET (green) can close voltage-dependent anion channels, or VDACs (center), passageways that allow metabolites and signaling molecules to pass through the outer membrane (blue band) of the mitochondria, the "power plant" that supplies cells with chemical energy. (Image courtesy of CTBP/Rice University)

Credit: CTBP/Rice University

In a study this week in the Proceedings of the National Academy of Sciences, an international team of researchers describe how a cancer-linked version of the protein mitoNEET can close the primary gateways in the outer surface of mitochondria, the "power plants" that supply cells with chemical energy.

These gateways, or "voltage-dependent anion channels" (VDACs), normally open and close to allow the passage of metabolites and other small molecules between mitochondria and the rest of the cell.

"The VDAC channel transports all types of metabolites between the cytosol and the mitochondria," said study co-author José Onuchic, a physicist and co-director of Rice University's Center for Theoretical Biological Physics (CTBP). "Dysfunction of this channel is involved in many diseases including cancer and fatty liver disease."

The research was performed by an international team of computational and structural biologists from CTBP, the University of California, San Diego (UCSD), the Hebrew University of Jerusalem and the University of Missouri-Columbia.

In the study, they detailed how mitoNEET regulates VDAC, and showed that the high-affinity interaction between the two proteins could be disrupted by a drug that targets VDAC.

"In its naturally occurring reduced state in healthy cells, mitoNEET has no measurable affinity for VDAC," said Onuchic, a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar in Cancer Research who led Rice's efforts on the project. "This indicates that the mechanism of interaction is redox-dependent and that targeting of the highly important VDAC complex in diseased states can be fine-tuned."

MitoNEET, a known player in cancer as well as diabetes, aging and Parkinson's disease, is a member of the NEET family of proteins, which transport clusters of iron and sulfur molecules inside cells. These clusters help regulate cells by controlling reduction-oxidation, or redox processes, and metabolism.

MitoNEET naturally adheres to the outer surface of the mitochondria, and the researchers said the direct connection of mitoNEET to VDAC, one of the most abundant proteins in the mitochondrial outer membrane, is significant.

Co-author Patricia Jennings, a structural biologist at UCSD, said, "The discovery that mitoNEET directly gates VDAC, the major porin of mitochondria, as well as the accompanying structural analysis and predictions for this interaction, affords a new platform for investigations of methods to induce cancer cells to commit cell suicide, or apoptosis/ferroptosis, in a cancer-specific, regulated process."

A defining characteristic of cancer progression is altered cellular metabolism. Study co-author Rachel Nechushtai of the Hebrew University said the work suggests it may be possible to regulate the metabolic and functional interactions of VDAC with a drug or drugs that could be useful against several kinds of cancer.

Onuchic said, "Fine-tuning a drug that specifically alters the redox-state of interaction between VDAC and mitoNEET would allow the development of new weapons to battle multiple cancers."

Nechushtai and Jennings first detailed the molecular structure of mitoNEET in 2007, and many of the collaborators on the project have worked together for more than a decade to decipher the workings of mitoNEET and related proteins like NAF-1 and MiNT.

"The junction of iron and redox is key to the control of many different cellular processes involved in many human pathologies," University of Missouri co-author Ron Mittler said. "Identifying a master point of regulation for these processes that is mediated by the mitoNEET-VDAC interaction is a major step forward in our understanding of these processes."

The researchers said longstanding ties between the collaborators and joint funding from both the US and Israel played a key role in the success of the project.

###

Additional co-authors are Colin Lipper and Jason Stofleth, both of UCSD; Yang Sung Sohn of the Hebrew University; and Fang Bai and Susmita Roy, both of Rice. Onuchic is the Harry C. and Olga K. Wiess Chair of Physics and a professor of physics and astronomy at Rice.

The research was supported by the National Science Foundation (1613462, 1427654, 1614101), the U.S.-Israel Binational Science Foundation (2015831), CPRIT, the University of Missouri, the Israel Cancer Research Fund, the Keck Center for Interdisciplinary Bioscience Training of the Gulf Coast Consortia and the National Institutes of Health (R01-GM101467).

High-resolution IMAGES are available for download at:

https://news-network.rice.edu/news/files/2019/09/0916-REDOX-mitoneet-JO22-lg.jpg
CAPTION: José Onuchic (Photo by Jeff Fitlow/Rice University)

https://news-network.rice.edu/news/files/2019/09/0916-REDOX-fig-lg.jpg
CAPTION: When oxidized, the protein mitoNEET (green) can close "voltage-dependent anion channels," or VDACs (center), passageways that allow metabolites and signaling molecules to pass through the outer membrane (blue band) of the mitochondria, the "power plant" that supplies cells with chemical energy. (Image courtesy of CTBP/Rice University)

Links and resources:

The DOI of the PNAS paper is: 10.1073/pnas.1908271116

A copy of the paper is available at: http://www.pnas.org/cgi/doi/10.1073/pnas.1908271116

This release can be found online at news.rice.edu.

Follow Rice News and Media Relations via Twitter @RiceUNews.

Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation's top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 3,962 undergraduates and 3,027 graduate students, Rice's undergraduate student-to-faculty ratio is just under 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice is ranked No. 1 for lots of race/class interaction and No. 4 for quality of life by the Princeton Review. Rice is also rated as a best value among private universities by Kiplinger's Personal Finance.

Media Contact

Jade Boyd
jadeboyd@rice.edu
713-348-6778

 @RiceUNews

http://news.rice.edu 

Jade Boyd | EurekAlert!
Further information:
http://dx.doi.org/10.1073/pnas.1908271116

Further reports about: CANCER Metabolism chemical energy metabolites mitochondria proteins

More articles from Health and Medicine:

nachricht Diabetes mellitus: A risk factor for early colorectal cancer
27.05.2020 | Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg

nachricht Ultra-thin fibres designed to protect nerves after brain surgery
27.05.2020 | Martin-Luther-Universität Halle-Wittenberg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Biotechnology: Triggered by light, a novel way to switch on an enzyme

In living cells, enzymes drive biochemical metabolic processes enabling reactions to take place efficiently. It is this very ability which allows them to be used as catalysts in biotechnology, for example to create chemical products such as pharmaceutics. Researchers now identified an enzyme that, when illuminated with blue light, becomes catalytically active and initiates a reaction that was previously unknown in enzymatics. The study was published in "Nature Communications".

Enzymes: they are the central drivers for biochemical metabolic processes in every living cell, enabling reactions to take place efficiently. It is this very...

Im Focus: New double-contrast technique picks up small tumors on MRI

Early detection of tumors is extremely important in treating cancer. A new technique developed by researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from normal tissue. The work is published May 25 in the journal Nature Nanotechnology.

researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from...

Im Focus: I-call - When microimplants communicate with each other / Innovation driver digitization - "Smart Health“

Microelectronics as a key technology enables numerous innovations in the field of intelligent medical technology. The Fraunhofer Institute for Biomedical Engineering IBMT coordinates the BMBF cooperative project "I-call" realizing the first electronic system for ultrasound-based, safe and interference-resistant data transmission between implants in the human body.

When microelectronic systems are used for medical applications, they have to meet high requirements in terms of biocompatibility, reliability, energy...

Im Focus: When predictions of theoretical chemists become reality

Thomas Heine, Professor of Theoretical Chemistry at TU Dresden, together with his team, first predicted a topological 2D polymer in 2019. Only one year later, an international team led by Italian researchers was able to synthesize these materials and experimentally prove their topological properties. For the renowned journal Nature Materials, this was the occasion to invite Thomas Heine to a News and Views article, which was published this week. Under the title "Making 2D Topological Polymers a reality" Prof. Heine describes how his theory became a reality.

Ultrathin materials are extremely interesting as building blocks for next generation nano electronic devices, as it is much easier to make circuits and other...

Im Focus: Rolling into the deep

Scientists took a leukocyte as the blueprint and developed a microrobot that has the size, shape and moving capabilities of a white blood cell. Simulating a blood vessel in a laboratory setting, they succeeded in magnetically navigating the ball-shaped microroller through this dynamic and dense environment. The drug-delivery vehicle withstood the simulated blood flow, pushing the developments in targeted drug delivery a step further: inside the body, there is no better access route to all tissues and organs than the circulatory system. A robot that could actually travel through this finely woven web would revolutionize the minimally-invasive treatment of illnesses.

A team of scientists from the Max Planck Institute for Intelligent Systems (MPI-IS) in Stuttgart invented a tiny microrobot that resembles a white blood cell...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

International Coral Reef Symposium in Bremen Postponed by a Year

06.04.2020 | Event News

 
Latest News

Black nitrogen: Bayreuth researchers discover new high-pressure material and solve a puzzle of the periodic table

29.05.2020 | Materials Sciences

Argonne researchers create active material out of microscopic spinning particles

29.05.2020 | Materials Sciences

Smart windows that self-illuminate on rainy days

29.05.2020 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>