Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING
JIB
GLOBETECH PUBLISHING

A Mitochondrial Transport Protein Protects Cancer Cells from Toxic Nanoparticles

By BiotechDaily International staff writers
Posted on 06 Jun 2013
Image: Senior author Dr. Priyabrata Mukherjee (Photo courtesy of the Mayo Clinic).
Image: Senior author Dr. Priyabrata Mukherjee (Photo courtesy of the Mayo Clinic).
A recent paper stressed the importance of linking the use of anticancer nanoparticle drugs and drug carriers to a basic understanding of the role of the mitochondria in the apoptotic process.

Cancer cells are surprisingly resistant to toxic effects of positively charged gold nanoparticles (+AuNPs). Investigators at the Mayo Clinic (Rochester, MN, USA) examined the interaction of +AuNPs with ovarian cancer cells growing in culture in order to determine the molecular mechanism protecting the cancer cells from the nanoparticles.

They reported in the April 24, 2013, online edition of the Journal of Biological Chemistry that the protein MICU1, a mitochondrial calcium uniporter, as a key molecule conferring cancer cells with resistance to +AuNPs. A uniporter is an integral membrane protein, either a channel or a carrier protein that is involved in facilitated diffusion. Uniporter carrier proteins work by binding to one molecule of solute at a time and transporting it with the solute gradient.

The MICU1 (mitochondrial calcium uptake 1) gene encodes an essential regulator of mitochondrial Ca2+ uptake under basal conditions. The encoded protein interacts with the mitochondrial calcium uniporter, a mitochondrial inner membrane Ca2+ channel, and is essential in preventing mitochondrial Ca2+ overload, which can cause excessive production of reactive oxygen species and cell stress.

The investigators found that in the ovarian cancer cells the increase in cytosolic Ca2+ induced by +AuNPs was balanced by MICU1, which prevented cell death. Silencing MICU1 decreased Bcl-2 (B-cell lymphoma 2), expression and increased caspase-3 activity and cytosolic cytochrome C levels—effects further enhanced in the presence of +AuNPs—thus initiating the mitochondrial pathway for apoptosis.

"This study identifies a novel mechanism that protects ovarian cancer cells by preventing the cell death, or apoptosis, which should occur when they encounter positively charged nanoparticles," said senior author Dr. Priyabrata Mukherjee, associate professor of biomedical engineering at the Mayo Clinic. "Furthermore, this work establishes MICU1 as a novel regulator of the apoptotic machinery in cancer cells and emphasizes the need to synergize nanoparticle design with understanding of mitochondrial machinery for enhancing targeted cellular toxicity."


Related Links:

Mayo Clinic



comments powered by Disqus

Channels

Drug Discovery

view channel
Image: Synthetic ion transporters can induce apoptosis by facilitating chloride anion transport into cells (Photo courtesy of the University of Texas, Austin).

Experimental Drug Kills Cancer Cells by Interfering with Their Ion Transport Mechanism

An experimental anticancer drug induces cells to enter a molecular pathway leading to apoptosis by skewing their ion transport systems to greatly favor the influx of chloride anions. To promote development... Read more

Therapeutics

view channel
Image: Liver cells regenerated in mice treated with a new drug (right) compared with a control group (center) after partial liver removal. Healthy liver cells are shown at left (Photo courtesy of Marshall et al, 2014, the Journal of Experimental Medicine).

New Drug Triggers Liver Regeneration After Surgery

Investigators have revealed that an innovative complement inhibitor decreases complement-mediated liver cell death, and actually stimulates postsurgery liver regrowth in mice. Liver cancer often results... Read more

Business

view channel

Partnership Established to Decode Bowel Disease

23andMe (Mountain View, CA,USA), a personal genetics company, is collaborating with Pfizer, Inc. (New York, NY, USA), in which the companies will seek to enroll 10,000 people with inflammatory bowel disease (IBD) in a research project designed to explore the genetic factors associated with the onset, progression, severity,... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.