Scientists find power switch for muscles

March 6, 2018, Salk Institute
Top left: PGC1 deficiency leads to severe muscle damage, evidenced by numerous centralized nuclei (highlighted with arrows), which is likely due to impaired mitochondrial energy metabolism (bottom left: blue staining shows impaired mitochondrial activity). Such muscle damage and mitochondrial impairment is largely rescued by ERRγ overexpression (top and bottom right). Credit: Salk Institute

If you've ever wondered how strenuous exercise translates into better endurance, researchers at the Salk Institute may have your answer. In a study published in the journal Cell Reports on March 6, 2018, scientists in Ronald Evans' lab have shown that the protein ERRγ (ERR gamma) helps deliver many of the benefits associated with endurance exercise.

"ERRγ helps make possible," says Ronald Evans, who is professor and director of the Gene Expression Laboratory and co-senior author on the paper. "It gears up the energy-creating cellular power plants known as , creating more blood vessels to bring in oxygen, take away toxins and help repair damage associated with muscle use. This makes ERRγ a really interesting potential therapeutic target for conditions with weakened muscles."

The story starts with the PGC1α and PGC1β proteins, which stimulate 20 other proteins associated with skeletal muscle energy and , including one from the Evans lab called ERRγ. In turn, ERRγ, a hormone receptor, acts to turn on genes. The Evans lab researchers wanted to precisely understand ERRγ's role in skeletal muscle energy production and how that impacts physical endurance.

To unravel this relationship, the Salk team studied mice without PGC1α/β. In some, they increased ERRγ selectively in . This approach allowed them to measure how ERRγ and PGC1 act independently, as well as how they function in combination.

Losing PGC1 had a negative impact on muscle energy and endurance. However, boosting ERRγ restored function. The team found ERRγ is essential to energy production, activating genes that create more mitochondria. In other words, they found the power switch for skeletal muscles.

The lab also showed that increased ERRγ in PGC1-deficient mice boosted their exercise performance. By measuring voluntary wheel running, they found that increasing ERRγ produced a five-fold increase in time spent exercising compared to mice with no PGC1 and normal ERRγ levels.

"Now that we have detected this direct target (ERRγ) for exercise-induced changes," says Weiwei Fan, a Salk research associate and the paper's first author, "we could potentially activate ERRγ and create the same changes that are being induced by exercise training."

In addition to increasing the number of mitochondria in skeletal muscle cells, ERRγ also increased muscular blood flow.

"You have to get more blood supply in to get more energy and take away toxic metabolites," says Michael Downes, a Salk senior scientist and co-senior author on the paper. "ERRγ boosts vascularization as well as mitochondria."

But perhaps the most important finding is that ERRγ could be a significant therapeutic target in helping to repair damaged muscles.

"Mitochondria play such a central role in cells throughout the body, but particularly in muscle cells, which tend to require more energy," says Evans. "We now know that, by increasing mitochondria output, ERRγ can actually rescue damaged . If we can identify small molecules that specifically target ERRγ, we hope to help people with muscular dystrophy and other conditions."

Explore further: Food for thought: Master protein enhances learning and memory

Related Stories

Food for thought: Master protein enhances learning and memory

April 7, 2015
Just as some people seem built to run marathons and have an easier time going for miles without tiring, others are born with a knack for memorizing things, from times tables to trivia facts. These two skills ― running and ...

Differences between 'marathon mice' and 'couch potato mice' reveal key to muscle fitness

May 8, 2013
Researchers discovered that small pieces of genetic material called microRNAs link the two defining characteristics of fit muscles: the ability to burn sugar and fat and the ability to switch between slow- and fast-twitch ...

Endurance training helpful in recovery from muscle inflammation, new study shows

November 8, 2017
Endurance training can actually be helpful in dealing with muscle inflammation, according to a new paper co-written by faculty at Binghamton University, State University of New York, and Karolinska Institutet and Karolinska ...

Scientists find new calorie-burning switch in brown fat

August 1, 2014
Biologists at The Scripps Research Institute (TSRI) have identified a signaling pathway that switches on a powerful calorie-burning process in brown fat cells.

New 'exercise hormone' promotes physical endurance

December 16, 2015
A new study in mice shows that exercise causes muscle to release a peptide that builds the muscle's capacity for energy production and increases physical endurance, allowing for longer and more intense exercise.

'Exercise-in-a-pill' boosts athletic endurance by 70 percent

May 2, 2017
Every week, there seems to be another story about the health benefits of running. That's great—but what if you can't run? For the elderly, obese or otherwise mobility-limited, the rewards of aerobic exercise have long been ...

Recommended for you

Female biology – two X chromosomes and ovaries – extends life and protects mice from aging

December 18, 2018
Around the world, women outlive men. This is true in sickness and in health, in war and in peace, even during severe epidemics and famine. In most animal species, females live longer than males.

Get a warrant: Researchers demand better DNA protections

December 18, 2018
New laws are required to control access to medical genetic data by law enforcement agencies, an analysis by University of Queensland researchers has found.

Wound care revolution: Put away your rulers and reach for your phone

December 18, 2018
Monitoring a wound is critical, especially in diabetic patients, whose lack of sensation due to nerve damage can lead to infection of a lesion and, ultimately, amputation. Clinicians and healthcare professionals at the McGill ...

Using light to stop itch

December 17, 2018
Itch is easily one of the most annoying sensations. For chronic skin diseases like eczema, it's a major symptom. Although it gives temporary relief, scratching only makes things worse because it can cause skin damage, additional ...

Law professor suggests a way to validate and integrate deep learning medical systems

December 13, 2018
University of Michigan professor W. Nicholson Price, who also has affiliations with Harvard Law School and the University of Copenhagen Faculty of Law, suggests in a Focus piece published in Science Translational Medicine, ...

Exercise-induced hormone irisin triggers bone remodeling in mice

December 13, 2018
Exercise has been touted to build bone mass, but exactly how it actually accomplishes this is a matter of debate. Now, researchers show that an exercise-induced hormone activates cells that are critical for bone remodeling ...

0 comments

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.