The role of DJ1 (PARK7) in regulating one-carbon metabolism to generate antioxidant capacities in colorectal cancer

• Applicant: Dr. Johannes Meiser
• Subject Area: Gastroenterology ; Biochemistry ; Cell Biology
• Term: from 2016 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 314131633

• Final Report Year: 2018

Final Report Abstract

In summary, my fellowship at the Beatson institute was extremely productive and extremely important for my scientific career. My observations put a new perspective on FOCM and cancer metabolism. I was able to uncover a new phenomenon related to serine catabolism and pinpoint this new metabolic pathway towards cancer cell invasion. The concept of formate overflow has additional implications in the context of normal cell physiology and in other cell types e.g. neurons (neurit formation and migration) or immune cells (invasion of immune cells). Moreover, the catabolic role of serine catabolism under certain microenvironmental conditions (for example glucose limitation) still needs to be explored. The fact that serine catabolism is located to the mitochondrion also fits nicely to the observations that mitochondria localise to the migration/invasion front of cells for localised energy supply.

Publications

• Serine one-carbon catabolism with formate overflow. Science Adv 2016, 2(10):e1601273
  Meiser J, Tumanov S, Maddocks O, Labuschagne CF, Athineos D, Van Den Broek N, Mackay GM, Gottlieb E, Blyth K, Vousden K et al.
  
• Mammals divert endogenous genotoxic formaldehyde into one-carbon metabolism. Nature. 2017;548(7669):549-54
  Burgos-Barragan G, Wit N, Meiser J, Dingler FA, Pietzke M, Mulderrig L, et al.
  
• Increased formate overflow is a hallmark of oxidative cancer. Nat Commun. 2018;9(1):1368
  Meiser J, Schuster A, Pietzke M, Vande Voorde J, Athineos D, Oizel K, et al.