Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Salk scientists find power switch for muscles

07.03.2018

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 endurance exercise 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 mitochondria, 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."


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

The story starts with the PGC1α and PGC1β proteins, which stimulate 20 other proteins associated with skeletal muscle energy and endurance exercise, 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 skeletal muscle cells. 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 energy output, ERRγ can actually rescue damaged muscle. If we can identify small molecules that specifically target ERRγ, we hope to help people with muscular dystrophy and other skeletal muscle conditions."

###

Other authors included Nanhai He, Chun Shi Lin, Zong Wei, Nasun Hah, Wanda Waizenegger, Ming-Xiao He, Ruth T. Yu and Annette R. Atkins at Salk and Christopher Liddle at Sydney Medical School.

This study was funded by: the Office of Naval Research (ONR N00014-16-1-3159), National Institutes of Health (DK057978, HL105278, HL088093, ES010337 and CA014195), National Institute of Environmental Health Sciences (P42ES010337), Department of the Navy, Office of Naval Research (N00014-16-1-3159), the National Health and Medical Research Council of Australia (512354 and 632886), The Leona M. and Harry B. Helmsley Charitable Trust (#2017PG-MED001), the Samuel Waxman Cancer Research Foundation, Ipsen/Biomeasure and the Glenn Foundation for Medical Research.

About the Salk Institute for Biological Studies:

Every cure has a starting point. The Salk Institute embodies Jonas Salk's mission to dare to make dreams into reality. Its internationally renowned and award-winning scientists explore the very foundations of life, seeking new understandings in neuroscience, genetics, immunology, plant biology and more. The Institute is an independent nonprofit organization and architectural landmark: small by choice, intimate by nature and fearless in the face of any challenge. Be it cancer or Alzheimer's, aging or diabetes, Salk is where cures begin. Learn more at: salk.edu.

Media Contact

Salk Communications
press@salk.edu
858-453-4100

 @salkinstitute

http://www.salk.edu 

Salk Communications | EurekAlert!

More articles from Life Sciences:

nachricht Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex

nachricht New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Graphene assembled film shows higher thermal conductivity than graphite film

22.06.2018 | Materials Sciences

Fast rising bedrock below West Antarctica reveals an extremely fluid Earth mantle

22.06.2018 | Earth Sciences

Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View

22.06.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>