Dr. Öğr. Üyesi Şükrü Anıl Doğan
Moleküler Biyoloji ve Genetik
Kuzey Park, 321
34342 Bebek - Istanbul
+90 (212) 359 4423
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Our research focuses on the investigation of mitochondrial involvement in stress signaling. We study different signals emanating from mitochondria and systematically dissect the molecular pathways those signals activate that may be exploited in the context of aging, age-related diseases and mitochondrial fitness.
Mitochondrial Dysfunction and Reactive Oxygen Species (ROS) Signaling in vivo
Mitochondria use oxygen to convert energy from nutrients into the cell’s major energy currency, ATP, through oxidative phosphorylation (OXPHOS). Because of their essential role in bioenergetics, impairment of mitochondria can lead to severe, often tissue-specific, disorders. Cells have developed various kinds of compensatory mechanisms, i.e. mitochondrial biogenesis, to counteract mitochondrial dysfunction, which play a central role in determining the extent of tissue-specific defects of disease phenotypes. In spite of recent progress, no specific therapy is currently available for OXPHOS disorders.
As the chief consumers of intracellular oxygen, mitochondria are the main source of reactive oxygen species (ROS), which are now being appreciated to have useful and beneficial effects such as signaling. ROS signaling controls a large number of transcriptional pathways; however, its importance in vivo has not been adequately investigated. When the redox equilibrium is disturbed due to the excessive accumulation or depletion of ROS, many cellular signaling pathways are influenced which confers to the cellular dysfunction and subsequently the development of various pathologies.
Currently, ROS-lowering interventions (such as antioxidants) are widely proposed as an anti-aging strategy in humans and used widely as therapy in some diseases. However, reducing the signaling ROS might be detrimental in some cases. We need to understand the under-studied physiological roles of ROS signaling to design better therapies for diseases and underline the potential hazards of unnecessary antioxidant use/treatment.
- Dogan SA, Cerutti R, Benincà C, Brea-Calvo G, Jacobs HT, Zeviani M, Szibor M, Viscomi C (2018) Perturbed Redox Signaling Exacerbates a Mitochondrial Myopathy. Cell Metab, 28: 1–12
- Aradjanski M, Dogan SA, Lotter S, Wang S, Hermans S, Wibom R, Rugarli E, Trifunovic A (2017) DARS2 protects against neuroinflammation and apoptotic neuronal loss, but is dispensable for myelin producing cells. Hum Mol Genet, 26: 4181–4189
- Bottani E, Cerutti R, Harbour ME, Ravaglia S, Dogan SA, Giordano C, Fearnley IM, D’Amati G, Viscomi C, Fernandez-Vizarra E, Zeviani M (2017) TTC19 Plays a Husbandry Role on UQCRFS1 Turnover in the Biogenesis of Mitochondrial Respiratory Complex III. Mol Cell, 67: 96–105.e4
- Kukat A, Dogan SA, Edgar D, Mourier A, Jacoby C, Maiti P, Mauer J, Becker C, Senft K, Wibom R, Kudin AP, Hultenby K, Flögel U, Rosenkranz S, Ricquier D, Kunz WS, Trifunovic A (2014) Loss of UCP2 attenuates mitochondrial dysfunction without altering ROS production and uncoupling activity. PLoS Genet, 10: e1004385
- Dogan SA, Pujol C, Maiti P, Kukat A, Wang S, Hermans S, Senft K, Wibom R, Rugarli EI, Trifunovic A (2014) Tissue-specific loss of DARS2 activates stress responses independently of respiratory chain deficiency in the heart. Cell Metab, 19: 458–469