Deciphering Molecular Mechanisms of Mitochondrial Stress Response in vivo

• Applicant: Professorin Dr. Aleksandra Trifunovic
• Subject Area: Cell Biology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 437779281

Maintenance of mitochondrial homeostasis is essential for a broad spectrum of signalling, metabolic and energetic processes. Consequently, mitochondrial dysfunction is linked to the development of a wide range of encephalomyopathies and many common diseases including type 2 diabetes, Parkinson’s and Alzheimer’s diseases. In response to disturbed mitochondrial proteostasis, the mitochondrial stress response (MSR) is initiated, which results in global adaptive transcriptional response and seems to partially share the signature of the integrated stress response (ISR). However, the interconnection of the two cascades remains uncharted. Furthermore, the exact sequence of events for different steps of the signalling cascade remains elusive. CHOP was the first transcription factor (TF) proposed to play a role in this process, although - due to the lack of a transactivating domain - it has to heterodimerize with other TFs to activate or suppresses its target genes. The overall goal of this study is to shed more light on the role of the MSR on cellular and organismal physiology, with specific focus on the molecular aspects and in vivo functions of CHOP in this process. We further want to identify CHOP's binding partner(s) and uncover its specific transcriptional targets. Finally, we want to understand the nature of signals upstream of the ISR and the interconnection of MSR with endoplasmic reticulum stress responses.

• DFG Programme: Research Grants