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Caffeine From Four Cups of Coffee Protects the Heart With the Help of Mitochondria

Summary: A new study reports caffeine concentration, the equivalent of four cups of coffee, can promote the movement of a regulatory protein into mitochondria. This can enhance mitochondrial function and protect heart cells from damage.

Source: PLOS.

Caffeine consumption has been associated with lower risks for multiple diseases, including type II diabetes, heart disease, and stroke, but the mechanism underlying these protective effects has been unclear. A new study now shows that caffeine promotes the movement of a regulatory protein into mitochondria, enhancing their function and protecting cardiovascular cells from damage.

The work, publishing 21 June in the open access journal PLOS Biology, by Judith Haendeler and Joachim Altschmied of the Medical Faculty, Heinrich-Heine-University and the IUF-Leibniz Research Institute for Environmental Medicine in Duesseldorf, Germany, and colleagues, found that the protective effect was reached at a concentration equivalent to consumption of four cups of coffee, suggesting the effect may be physiologically relevant.

The authors have previously shown that at physiologically relevant concentrations (i.e. levels reached after four or more cups of coffee) caffeine improved the functional capacity of endothelial cells, which line the interior of blood vessels, and that the effect involved mitochondria, the cell’s energy powerhouses.

Here, they showed that a protein called p27, known mainly as an inhibitor of the cell cycle, was present in mitochondria in the major cell types of the heart. In these cells, mitochondrial p27 promoted migration of endothelial cells, protected heart muscle cells from cell death, and triggered the conversion of fibroblasts into cells containing contractile fibers — all crucial for repair of heart muscle after myocardial infarction. They found that caffeine induced the movement of p27 into mitochondria, setting off this beneficial chain of events, and did so at a concentration that is reached in humans by drinking four cups of coffee. Caffeine was protective against heart damage in pre-diabetic, obese mice, and in aged mice.

a cup of coffee with a heart in the foam

They found that caffeine induced the movement of p27 into mitochondria, setting off this beneficial chain of events, and did so at a concentration that is reached in humans by drinking four cups of coffee. NeuroscienceNews.com image is in the public domain.

“Our results indicate a new mode of action for caffeine,” said Haendeler, “one that promotes protection and repair of heart muscle through the action of mitochondrial p27. These results should lead to better strategies for protecting heart muscle from damage, including consideration of coffee consumption or caffeine as an additional dietary factor in the elderly population. Furthermore, enhancing mitochondrial p27 could serve as a potential therapeutic strategy not only in cardiovascular diseases but also in improving healthspan.”

About this neuroscience research article

Source: PLOS
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Open access research for “CDKN1B/p27 is localized in mitochondria and improves respiration-dependent processes in the cardiovascular system—New mode of action for caffeine” by Niloofar Ale-Agha, Christine Goy, Philipp Jakobs, Ioakim Spyridopoulos, Stefanie Gonnissen, Nadine Dyballa-Rukes, Karin Aufenvenne, Florian von Ameln, Mark Zurek, Tim Spannbrucker, Olaf Eckermann, Sascha Jakob, Simone Gorressen, Marcel Abrams, Maria Grandoch, Jens W. Fischer, Karl Köhrer, René Deenen, Klaus Unfried, Joachim Altschmied, and Judith Haendeler in PLOS Biology. Published June 21 2018.
doi:10.1371/journal.pbio.2004408

Cite This NeuroscienceNews.com Article
PLOS”Caffeine From Four Cups of Coffee Protects the Heart With the Help of Mitochondria.” NeuroscienceNews. NeuroscienceNews, 22 June 2018.
<http://neurosciencenews.com/caffeine-mitochondria-heart-9417/>.
PLOS(2018, June 22). Caffeine From Four Cups of Coffee Protects the Heart With the Help of Mitochondria. NeuroscienceNews. Retrieved June 22, 2018 from http://neurosciencenews.com/caffeine-mitochondria-heart-9417/
PLOS”Caffeine From Four Cups of Coffee Protects the Heart With the Help of Mitochondria.” http://neurosciencenews.com/caffeine-mitochondria-heart-9417/ (accessed June 22, 2018).

Abstract

CDKN1B/p27 is localized in mitochondria and improves respiration-dependent processes in the cardiovascular system—New mode of action for caffeine

We show that the cyclin-dependent kinase inhibitor 1B (CDKN1B)/p27, previously known as a cell cycle inhibitor, is also localized within mitochondria. The migratory capacity of endothelial cells, which need intact mitochondria, is completely dependent on mitochondrial p27. Mitochondrial p27 improves mitochondrial membrane potential, increases adenosine triphosphate (ATP) content, and is required for the promigratory effect of caffeine. Domain mapping of p27 revealed that the N-terminus and C-terminus are required for those improvements. Further analysis of those regions revealed that the translocation of p27 into the mitochondria and its promigratory activity depend on serine 10 and threonine 187. In addition, mitochondrial p27 protects cardiomyocytes against apoptosis. Moreover, mitochondrial p27 is necessary and sufficient for cardiac myofibroblast differentiation. In addition, p27 deficiency and aging decrease respiration in heart mitochondria. Caffeine does not increase respiration in p27-deficient animals, whereas aged mice display improvement after 10 days of caffeine in drinking water. Moreover, caffeine induces transcriptome changes in a p27-dependent manner, affecting mostly genes relevant for mitochondrial processes. Caffeine also reduces infarct size after myocardial infarction in prediabetic mice and increases mitochondrial p27. Our data characterize mitochondrial p27 as a common denominator that improves mitochondria-dependent processes and define an increase in mitochondrial p27 as a new mode of action of caffeine.

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