Role of mitochondrial Telomerase Reverse Transcriptase and mitochondrial p27 in myocardial infarction

We will investigate the functions of mitochondrial p27 in the early phase after I/R in vivo in mice containing p27 exclusively in the mitochondria and by applying a recombinant cell-penetrating mitochondrially targeted p27. Furthermore, we will assess if the telomerase activator TA-65 can improve the outcomes after I/R. The role of mitochondrial p27 and mitochondrial TERT will also be explored in mice on a diabetogenic diet. Furthermore, we will prove the concept of potential common upstream regulators of both proteins. Finally, we will characterize their mitochondrial interactome and the impact of both proteins on the transcriptome.

Project related publications

Ottolini M*, Hong K*, Cope EL, Daneva Z, DeLalio LJ, Sokolowski JD, Marziano C, Nguyen NY, Altschmied J, Haendeler J, Johnstone SR, Kalani MY, Park MS, Patel RP, Liedtke W, Isakson BE, Sonkusare SK. Local peroxynitrite impairs endothelial Transient Receptor Potential Vanilloid 4 channels and elevates blood pressure in obesity. Circulation. 2020;141:1318-1333
*equal contribution

Rosen J*, Jakobs P*, Ale-Agha N, Altschmied J¶, Haendeler J¶. Non-canonical functions of Telomerase Reverse Transcriptase – impact on redox homeostasis. Redox Biol. 2020 in press
*equal contribution ¶corresponding authors

Grandoch M, Flögel U, Virtue S, Maier JK, Jelenik T, Kohlmorgen C, Feldmann K, Ostendorf Y, Castañeda TR, Zhou Z, Yamaguchi Y, Nascimento EBM, Sunkari VG, Goy C, Kinzig M, Sörgel F, Bollyky PL, Schrauwen P, Al-Hasani H, Roden M, Keipert S, Vidal-Puig A, Jastroch M, Haendeler J, Fischer JW. 4-Methylumbelliferone improves the thermogenic capacity of brown adipose tissue. Nat Metab. 2019;5:546-559

Nguyen TD, Schwarzer M, Schrepper A, Amorim PA, Blum D, Hain C, Faerber G, Haendeler J, Altschmied J, Doenst T. Increased Protein Tyrosine Phosphatase 1B (PTP1B) Activity and Cardiac Insulin Resistance Precede Mitochondrial and Contractile Dysfunction in Pressure-Overloaded Hearts. J Am Heart Assoc. 2018;7

Hendgen-Cotta UB, Esfeld S, Jastrow H, Totzeck M, Altschmied J, Goy C, Haendeler J, Winterhager E, Rassaf T. Mouse cardiac mitochondria do not separate in subsarcolemmal and interfibrillar subpopulations. Mitochondrion. 2018;38:1-5.

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, Kohrer K, Deenen R, Unfried K, Altschmied J, Haendeler J. CDKN1B/p27 is localized in mitochondria and improves respiration-dependent processes in the cardiovascular system-New mode of action for caffeine. PLoS Biol. 2018;16:e2004408.

Heiss C, Spyridopoulos I, Haendeler J. Interventions to slow cardiovascular aging: Dietary restriction, drugs and novel molecules. Exp Gerontol. 2017;
Zurek M, Altschmied J, Kohlgrüber S, Ale-Agha N, Haendeler J. Role of Telomerase in the Cardiovascular System. Genes (Basel). 2016;7:29.

Eckers A, Jakob S, Heiss C, Haarmann-Stemmann T, Goy C, Brinkmann V, Cortese-Krott MM, Sansone R, Esser C, Ale-Agha N, Altschmied J, Ventura N, Haendeler J. The aryl hydrocarbon receptor promotes aging phenotypes across species. Sci Rep. 2016;6:19618.

Eckers A, Haendeler J. Endothelial cells in health and disease. Antioxid Redox Signal. 2015;22:1209-11.

Postdoctoral researcher

Dr. rer. nat. Niloofar Ale-Agha

Principal Investigator

Prof. Dr. rer. nat. Judith Haendeler

Environmentally-induced cardiovascular degeneration Institute of Clinical Chemistry and Laboratory Diagnostics Medical Faculty, University of Düsseldorf
IUF - Leibniz Research Institute for Environmental Medicine
Phone +49 211 3389291
Fax +49 211 3389331

Principal Investigator

Prof. Dr. rer.nat Joachim Altschmied

IUF - Leibniz Research Institute for Environmental Medicine
Phone +49 211 3389315
Fax +49 211-3389331
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