ArticlePLoS biology2018
CDKN1B/p27 is localized in mitochondria and improves respiration-dependent processes in the cardiovascular system-New mode of action for caffeine.
Article in PLoS biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Cardiovascular inflammaging: Mechanisms, consequences, and therapeutic perspectives.Cell reports. Medicine · 2025Review
- Caffeine Protects Keratinocytes fromInternational journal of molecular sciences · 2024Article
- Association of caffeine consumption with all-cause and cause-specific mortality in adult Americans with hypertension.Food science & nutrition · 2024Article
- Dose-Dependent Effects of Lipopolysaccharide on the Endothelium-Sepsis versus Metabolic Endotoxemia-Induced Cellular Senescence.Antioxidants (Basel, Switzerland) · 2024Review
- Therapeutic Potential of Targeting p27Archives of internal medicine research · 2024Article
- Caffeine Inhibits Oxidative Stress- and Low Dose Endotoxemia-Induced Senescence-Role of Thioredoxin-1.Antioxidants (Basel, Switzerland) · 2023Article
- Aryl Hydrocarbon Receptor-Dependent and -Independent Pathways Mediate Curcumin Anti-Aging Effects.Antioxidants (Basel, Switzerland) · 2022Article
- Advances in Stigmasterol on its anti-tumor effect and mechanism of action.Frontiers in oncology · 2022Review
- Caffeine promotes angiogenesis through modulating endothelial mitochondrial dynamics.Acta pharmacologica Sinica · 2021Article
- Association between Caffeine Intake and All-Cause and Cause-Specific Mortality: An Analysis of the National Health and Nutrition Examination Survey (NHANES) 1999-2014 Database.Nursing reports (Pavia, Italy) · 2021Article
- Selenoprotein T Protects Endothelial Cells against Lipopolysaccharide-Induced Activation and Apoptosis.Antioxidants (Basel, Switzerland) · 2021Article
- The AMPK/p27Cells · 2021Review
- Consumer Choices and Habits Related to Coffee Consumption by Poles.International journal of environmental research and public health · 2021Article
- A cancer-associated CDKN1B mutation induces p27 phosphorylation on a novel residue: a new mechanism for tumor suppressor loss-of-function.Molecular oncology · 2021Article
- Extra-Nuclear Functions of the Transcription Factor Grainyhead-Like 3 in the Endothelium-Interaction with Endothelial Nitric Oxide Synthase.Antioxidants (Basel, Switzerland) · 2021Article
- The Selectivity for Tumor Cells of Nuclear-Directed Cytotoxic RNases Is Mediated by the Nuclear/Cytoplasmic Distribution of p27Molecules (Basel, Switzerland) · 2021Article
- Effects of Dietary Supplements on Adaptations to Endurance Training.Sports medicine (Auckland, N.Z.) · 2020Review
- Cardiac fibroblast activation and hyaluronan synthesis in response to hyperglycemia and diet-induced insulin resistance.Scientific reports · 2019Article
- High Concentration of Low-Density Lipoprotein Results in Disturbances in Mitochondrial Transcription and Functionality in Endothelial Cells.Oxidative medicine and cellular longevity · 2019Article
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Corrections and comments
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Authors and funding
21 authors at 3 institutions in 2 countries.
Funding
Abstract
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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Registered trials
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