Systemic evaluation of MYC dependent mitochondrial activity

Gyorgy Szabadkai (primary)
Department of Cell Developmental Biology
University College London
Mariia Yuneva (secondary)
Oncogenes and Tumour Metabolism Laboratory
The Francis Crick Institute


Myc master regulates a large fraction of the genome, but also has tight control on cell function and fate via effecting essential metabolic pathways. Mitochondria harbour several other essential pathways, recently classified in seven large functional groups. Whether these essential pathways are controlled by Myc, has not been established, and the main objective of the project, which will use genetic Myc models for (i) gathering, processing and modelling data covering the transcriptome, metabolome, flux analysis, lipidome. These data will be combined with (ii) advanced in vivo tumour tissue imaging to determine mitochondrial morphology and function with a range of assays.


1. Pellanda P, Dalsass M, Filipuzzi M, Loffreda A, Verrecchia A, Castillo Cano V, Thabussot H, Doni M, Morelli MJ, Soucek L, Kress T. Integrated requirement of non-specific and sequence-specific DNA binding in Myc-driven transcription. EMBO J. 2021 17;40(10)
2. Meyer N, Penn LZ. Reflecting on 25 years with MYC. Nat Rev Cancer 2008; 8: 976–990.
3. Dejure FR, Eilers M. MYC and tumor metabolism: chicken and egg. The EMBO Journal 2017; 36: 3409–3420.
4. Rath S, Sharma R, Gupta R, Ast T, Chan C, Durham TJ, Goodman RP, Grabarek Z, Haas ME, Hung WHW, Joshi PR, Jourdain AA, Kim SH, Kotrys AV. MitoCarta3.0: an updated mitochondrial proteome now with sub-organelle localization and pathway annotations. Nucleic Acids Res. 2021 8;49(D1):D1541-D1547
5. Morrish F, Hockenbery D. MYC and mitochondrial biogenesis Cold Spring Harb Perspect Med. 2014 1;4(5):a014225
6.Yuneva MO, Fan TWM, Allen TD, Higashi RM, Ferraris D V., Tsukamoto T, Matés JM, Alonso FJ, Wang C, Seo Y, Chen X, Bishop JM. The Metabolic Profile of Tumors Depends on Both the Responsible Genetic Lesion and Tissue Type. Cell Metab 2012; 15: 157–170.
7. Méndez-Lucas A, Lin W, Driscoll PC, Legrave N, Novellasdemunt L, Xie C, Charles M, Wilson Z, Jones NP, Rayport S, Rodríguez-Justo M, Li V, et al. Identifying strategies to target the metabolic flexibility of tumours. Nat Metab 2020; 2: 335–350.
8. Blacker TS, Mann ZF, Gale JE, Ziegler M, Bain AJ, Szabadkai G, Duchen MR. Separating NADH and NADPH fluorescence in live cells and tissues using FLIM. Nat Commun 2014; 5: 1–9.
9. Levitt JA, Poland SP, Krstajic N, Pfisterer K, Erdogan A, Barber PR, Parsons M, Henderson RK, Ameer-Beg SM. Quantitative real-time imaging of intracellular FRET biosensor dynamics using rapid multi-beam confocal FLIM. Sci Rep 2020; 10: 1–9.

Molecules, cells and industrial biotechnology
Area of Biology
Cell BiologyChemical Biology
Techniques & Approaches
BiochemistryBioinformaticsChemistryImage ProcessingMicroscopy / ElectrophysiologyMolecular BiologySimulation / Modelling