MicroRNAs regulate the formation of mitochondria in cells

April 9, 2018, Max Planck Society

Muscles require a large amount of energy to function. This is provided primarily by mitochondria in cells that consume a lot of energy. We therefore find more of these powerhouses of the cell in muscle cells than in other cell types with a lower metabolic rate. Scientists at the Max Planck Institute for Heart and Lung Research in Bad Nauheim have now identified a mechanism that can be used to regulate the development of mitochondria in muscle cells. This is what makes the endurance capacity of muscles even possible in the first place.

Energy is supplied to via two different mechanisms: by means of a process known as glycolysis, cells extract the energy carrier adenosine triphosphate (ATP) from glucose. Oxygen is not required. The disadvantage of glycolysis is its low efficiency. For this reason, cells that require a lot of energy to function manufacture ATP primarily via the respiratory chain. This is more efficient than glycolysis. It takes place in the mitochondria and consumes oxygen. Due to their relatively high energy demand, require a particularly high number of mitochondria compared to other cell types.

Scientists in Thomas Braun's "Cardiac Development and Remodelling" Department have now discovered a mechanism that controls the formation of mitochondria during muscle stem cell differentiation into functional muscle cells. Short, non-coding RNA molecules, known as microRNAs, play a crucial role in this process, as a does a group of known as a mega gene . Thomas Böttger, Group Leader in the Department at the Max Planck Institute explains how it works: "In , the Dlk1-Dio3 gene cluster blocks the formation of mitochondria. This retains the carefully orchestrated balance of energy metabolism in these cells."

New mitochondria for muscle cells

If stem cells develop into muscle cells, the energy demand changes dramatically. A large number of mitochondria are formed within a short space of time. "We were able to show that the mega gene cluster is active in stem cells but not in any of the differentiated somatic cells that we studied," says Böttger. The Max Planck researchers concluded from this that the mega gene cluster is switched off during cell differentiation.

Evidence of the underlying mechanism emerged when the scientists studied in greater depth the differentiation of stem cells into muscle cells: "In parallel with the slow-down in the Dlk1-Dio3 gene cluster, we noted an increase in two non-coding microRNAs, namely miR-1 and miR-133a," says Böttger. When miR-1 and miR-133a were switched off in the muscle cells in the experiment, the individual components of the mega gene cluster could be shown in these cells. "This is a strong indication that miR-1 and miR-133a prevent the formation of the mega gene cluster," says Böttger. "If both microRNAs are absent, the mega gene cluster remains active. In fact, we then observed a decrease in mitochondrial genes and atypical mitochondria."

Studies on mice in which the genes for miR-1 and miR-133a were genetically knocked out confirmed the data: "Significantly fewer mitochondria were found in the muscle cells of miR-1/miR-133a knockout mice compared to the muscle cells of the control animals. While maintaining the same strength, we noted a significantly reduced endurance capacity among the knockout mice," says Böttger.

The researchers' proposed the following explanation for this phenomenon: while the for short-term muscle activity is provided anaerobically via glycolysis, aerobic processes are required for endurance. "The muscles need sufficient mitochondria for sustained muscle activity," says Böttger. "Our study shows that the two microRNAs – miR-1/miR-133a – deactivate the mega gene cluster during the formation of cells from stem cells and as a result the formation of large numbers of is possible." The study thus makes an important contribution to understanding the transformation of stem cells into somatic cells.

Explore further: Oestrogen receptor causes weight loss in male mice

More information: Stas Wüst et al. Metabolic Maturation during Muscle Stem Cell Differentiation Is Achieved by miR-1/133a -Mediated Inhibition of the Dlk1-Dio3 Mega Gene Cluster, Cell Metabolism (2018). DOI: 10.1016/j.cmet.2018.02.022

Related Stories

Oestrogen receptor causes weight loss in male mice

April 13, 2017

Muscles consume a large part of the body's energy. Hence when fat metabolism in muscle cells is impaired, the organism gains weight. Scientists from the Max Planck Institute for Heart and Lung Research in Bad Nauheim have ...

Study tracks protein's role in stem cell function

March 23, 2018

MCL-1 is a member of the BCL-2 family of proteins important for blocking apoptosis, or programmed cell death. Many types of cancer cells escape the body's effort to kill them by overexpressing MCL-1.

Scientists find power switch for muscles

March 6, 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 ...

How to reap the benefits of exercise: It's in the genes

January 10, 2017

An international team of scientists at Baylor College of Medicine, the Telethon Institute of Genetics and Medicine in Naples, Italy and other institutions has discovered that the gene TFEB is a major regulator of muscle function ...

Recommended for you

Two new planets discovered using artificial intelligence

March 26, 2019

Astronomers at The University of Texas at Austin, in partnership with Google, have used artificial intelligence (AI) to uncover two more hidden planets in the Kepler space telescope archive. The technique shows promise for ...

Infertility's roots in DNA packaging

March 26, 2019

Pathological infertility is a condition affecting roughly 7 percent of human males, and among those afflicted, 10 to 15 percent are thought to have a genetic cause. However, pinpointing the precise genes responsible for the ...

Facebook is free, but should it count toward GDP anyway?

March 26, 2019

For several decades, gross domestic product (GDP), a sum of the value of purchased goods, has been a ubiquitous yardstick of economic activity. More recently, some observers have suggested that GDP falls short because it ...

Droughts could hit aging power plants hard

March 26, 2019

Older power plants with once-through cooling systems generate about a third of all U.S. electricity, but their future generating capacity will be undercut by droughts and rising water temperatures linked to climate change. ...


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.