To survey previously uncharted territory, a team of researchers at UW-Madison created an “atlas” that maps more than 1,500 unique landmarks within mitochondria that could provide clues to the metabolic connections between caloric restriction and aging.
The map, as well as the techniques used to create it, could lead to a better understanding of how cell metabolism is re-wired in some cancers, age-related diseases and metabolic conditions such as diabetes.
“It’s really a dynamic atlas for regulatory points in mitochondrial function -- there are many interesting avenues that other scientists can follow up on,” says John Denu, professor of biomolecular chemistry and leader of the Epigenetics theme at the Wisconsin Institute for Discovery (WID). “It could take years for researchers to understand what it all means, but at least now we have a list of the most important players.”
In previous experiments, it’s been shown that consuming less food increases the life span and health span in a range of organisms, from yeast and flies to mice and non-human primates. But pinpointing where and how caloric restriction affects cells at a molecular level remains the challenge.
So far, mitochondrial proteins, the molecules that command specific actions in the cell’s powerhouse organelle, are at center stage of metabolic reprogramming.
Denu and colleagues conducted earlier research on the mitochondrial protein Sirt3, where they suggested a link between Sirt3 and the benefits of caloric restriction in situations such as the prevention of age-related hearing loss.
The new research, published in the Nov. 29 issue of the journal Molecular Cell, more broadly identifies pathways in mitochondria that could be behind the re-wiring of metabolism. Their work uncovered regulatory processes that maintain mitochondrial health, control cells’ ability to metabolize fat and amino acids, as well as stimulate anti-oxidant responses. This re-wiring involves the addition or removal of two-carbon (acetylation) chemical groups within regulatory molecules called proteins.
In the study, scientists looked at liver tissue from groups of mice -- both with and without the ability to produce Sirt3. Some received a calorically restricted diet and some did not. After one year, they compared protein and acetylation changes among the groups of mice. They found Sirt3 was essential for many of the metabolic adaptations that occur during calorie restriction. These results suggest that therapies, including diet or drugs that enhance Sirt3 function, might provide novel interventions to fend off age-related illnesses.
Joshua Coon, professor of chemistry and biomolecular chemistry at UW-Madison and co-author of the paper, crafted a new technique to find these molecular sites. While the genome plays a key role in an organism’s health, he points out that studying proteins -- the molecular machines that carry out an organism’s original genetic instructions -- can be more accurate in revealing how a gene functions.
“We’ve taken dozens of primary tissues and profiled their protein content with depth to learn how they vary,” Coon says. “With that information, we have direct knowledge at the molecular level of how an organism is dealing with adaption to diet, or potentially, a given disease state.”
He says using mass spectrometry to look for acetylated proteins from tissue samples is a more fruitful approach to identify relevant physiological changes. The study, he says, is one of the first of many that will create descriptive maps for other disease models.
To expand access to these enabling technologies across campus, Coon plans to launch the Wisconsin Center for Collaborative Proteomics in 2013. The center has received significant support from the UW and is pending further support via federal funding.
-- Marianne English, 608-316-4687, firstname.lastname@example.org
John Denu, 608-316-4341, email@example.com; Joshua Coon, 608-263-1718, firstname.lastname@example.org
Marianne English | Newswise Science News
Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
30.03.2017 | Health and Medicine
30.03.2017 | Health and Medicine
30.03.2017 | Medical Engineering