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Ale-Agha 2018 PLOS Biol
Additional label Labels  + , 2018-08  +
Coupling states OXPHOS  +
Has abstract We show that the cyclin-dependent kinase i
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.
l p27 as a new mode of action of caffeine.  +
Has editor [[Plangger M]]  + , [[Kandolf G]]  +
Has info [ PMID: 29927970 Open Access]  +
Has title Ale-Agha N, Goy C, Jakobs P, Spyridopoulos
Ale-Agha N, Goy C, Jakobs P, Spyridopoulos I, Gonnissen S, Dyballa-Rukes N, Aufenvenne K, von Ameln F, Zurek M, Spannbrucker T, Eckermann O, Jakob S, Gorressen S, Abrams M, Grandoch M, Fischer JW, Köhrer K, Deenen R, Unfried K, Altschmied J, Haendeler J (2018) CDKN1B/p27 is localized in mitochondria and improves respiration-dependent processes in the cardiovascular system - New mode of action for caffeine. PLOS Biol 6:e2004408.
action for caffeine. PLOS Biol 6:e2004408.  +
Instrument and method Oxygraph-2k  +
Mammal and model Mouse  +
MiP area Respiration  + , nDNA;cell genetics  + , Pharmacology;toxicology  +
Pathways N  + , S  + , CIV  +
Preparation Isolated mitochondria  +
Tissue and cell Heart  +
Was published by MiPNetLab DE Duesseldorf Haendeler J +
Was published in journal PLOS Biol +
Was published in year 2018  +
Was written by Ale-Agha N + , Goy C + , Jakobs P + , Spyridopoulos I + , Gonnissen S + , Dyballa-Rukes N + , Aufenvenne K + , Von Ameln F + , Zurek M + , Spannbrucker T + , Eckermann O + , Jakob S + , Gorressen S + , Abrams M + , Grandoch M + , Fischer JW + , Koehrer K + , Deenen R + , Unfried K + , Altschmied J + , Haendeler J +
Categories Publications
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
13:45:44, 23 August 2018  +
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