Researchers examine metabolism in defective cells

April 11, 2014

University of Alberta researchers are taking a closer look at how two metabolic pathways interact to increase the lifespan of cells with mitochondrial defects. Magnus Friis is the lead author of the study, which was published online on April 10 and will be published in the April 24 issue of Cell Reports.

Mitochondria produce energy for cells through oxidative metabolism, but the process produces toxic byproducts that can accumulate and cause defects in the cell's mitochondria. These defects, in turn, affect the cell's ability to generate energy and can potentially lead to and are associated with aging and various neurological diseases.

Friis, a postdoctoral fellow in Mike Schultz's biochemistry lab, examined how dietary changes at the cell level can affect cell health. He exposed normal and defective yeast cells to two different energy sources: glucose, the preferred sugar of cells, and raffinose, a natural sugar found in vegetables and whole grains.

"[The dietary intervention] is a general shift in what we're feeding the cells to get them to do something different with their whole nutrient metabolism," Friis noted. "There are signaling pathways that allow a cell to sense its environment and co-ordinate events to allow the cell to adapt to what's going on. In this case, [cells are responding to] which nutrients are available."

Friis and Schultz examined two nutrient signaling pathways called the AMPK pathway and the retrograde response. AMPK responds to energy deficits in the cell by down-regulating energy consuming processes, which are often associated with cell growth, and up-regulating energy producing processes. The retrograde response pathway is specific to the yeast used in the study and supplies key amino acids to the cell by changing the metabolic process of the mitochondria.

When activated individually, neither the AMPK pathway nor the retrograde response provided substantial benefits to cells with damaged mitochondria. When activated simultaneously, clear benefits became evident.

"We looked at the effect activating both pathways had on maintenance of cellular viability in what's called a chronological aging experiment," Friis said. "Even when they had defective mitochondria, the cells with the retrograde response and AMPK simultaneously activated during growth were able to live as long as cells with normal mitochondrial function."

Working in collaboration with John Paul Glaves, a in Bryan Sykes' lab, and Tao Huan, a PhD student in Liang Li's lab, Friis measured the molecules produced during the . They found that the defective cells had higher levels of branched chain and trahelose, a carbohydrate found in yeast that can serve an energy source, similar to glycogen in human cells.

"By activating AMPK, we've removed certain blocks in metabolism. With the retrograde response, we've changed the amino acid metabolism in a way that allowed the to accumulate storage carbohydrates, which stabilize their function," Friis said.

Activated AMPK and retrograde response pathways allow the cell to accumulate a storage carbohydrate, which can be metabolize normally despite that affect the cell's metabolism. The additional energy stabilizes cell function and prevents premature cell death often caused by defects in mitochondria.

"No matter how many people are working on the problem in humans, mitochondrial disorders are too complicated to figure out the nuts and bolts without the work that Magnus is doing," Schultz said. "This research opens the concept, a new concept on how to deal with these metabolic problems."

Explore further: Cancer cell metabolism kills

Related Stories

Cancer cell metabolism kills

April 15, 2013
Adenosine-5'-triphosphate (ATP) is the main energy source for all forms of work inside our cells. Scientists from the University of Helsinki, Finland, have found that even a short-term shortage of ATP supply can be fatal ...

Scientists find potential target for treating mitochondrial disorders

March 27, 2014
Mitochondria, long known as "cellular power plants" for their generation of the key energy source adenosine triphosphate (ATP), are essential for proper cellular functions. Mitochondrial defects are often observed in a variety ...

Gene links obesity and immunity

August 16, 2013
Auckland scientists have discovered a gene that links the immune system with obesity and potentially a new pathway to fight the worldwide obesity epidemic.

Cellular fuel gauge may hold the key to restricting cancer growth

December 27, 2012
Researchers at McGill University have discovered that a key regulator of energy metabolism in cancer cells known as the AMP-activated protein kinase (AMPK) may play a crucial role in restricting cancer cell growth. AMPK acts ...

Cell metabolism discovery could lead to treatments for cancer, common cold

April 2, 2014
(Medical Xpress)—Scientists at UCLA's Jonsson Comprehensive Cancer Center have published the first study explaining in detail how viruses reprogram the metabolism of the cells they invade to promote continued viral growth ...

Classic signaling pathway holds the key to prostate cancer progression

December 20, 2013
University of Houston researchers published a study investigating the processes through which androgen receptors affect prostate cancer progression. The publication, "Androgens Regulate Prostate Cancer Cell Growth via an ...

Recommended for you

Researchers describe mechanism that underlies age-associated bone loss

September 22, 2017
A major health problem in older people is age-associated osteoporosis—the thinning of bone and the loss of bone density that increases the risk of fractures. Often this is accompanied by an increase in fat cells in the ...

Researchers develop treatment to reduce rate of cleft palate relapse complication

September 22, 2017
Young people with cleft palate may one day face fewer painful surgeries and spend less time undergoing uncomfortable orthodontic treatments thanks to a new therapy developed by researchers from the UCLA School of Dentistry. ...

Exosomes are the missing link to insulin resistance in diabetes

September 21, 2017
Chronic tissue inflammation resulting from obesity is an underlying cause of insulin resistance and type 2 diabetes. But the mechanism by which this occurs has remained cloaked, until now.

Thousands of new microbial communities identified in human body

September 20, 2017
A new study of the human microbiome—the trillions of microbial organisms that live on and within our bodies—has analyzed thousands of new measurements of microbial communities from the gut, skin, mouth, and vaginal microbiome, ...

Study finds immune system is critical to regeneration

September 20, 2017
The answer to regenerative medicine's most compelling question—why some organisms can regenerate major body parts such as hearts and limbs while others, such as humans, cannot—may lie with the body's innate immune system, ...

Immune cells produce wound healing factor, could lead to new IBD treatment

September 20, 2017
Specific immune cells have the ability to produce a healing factor that can promote wound repair in the intestine, a finding that could lead to new, potential therapeutic treatments for inflammatory bowel disease (IBD), according ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

JVK
1 / 5 (2) Apr 11, 2014
Nutrient-dependent ecological adaptations in yeasts and other species are pheromone-controlled by the conserved molecular mechanisms that link the epigenetic landscape to the physical landscape of DNA. Ecological, social, neurogenic,and socio-cognitive niche construction are exemplified via amino acid substitutions that link yeasts to increasing organismal complexity.

Nutrient-dependent/pheromone-controlled adaptive evolution: a model
http://www.socioa...53/27989

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.