Neuzil 2022 Abstract Bioblast

From Bioblast
Jump to navigation Jump to search
Neuzil Jiri
Endaya BB, Le TDD, Kucera L, Lopes Oliveira G, Neuzil Jiri (2022) Metabolic switch supports proliferation in regenerating liver. Bioblast 2022: BEC Inaugural Conference.

Link: Bioblast 2022: BEC Inaugural Conference

Endaya Berwini B, Le Thi Dan Diem, Kucera Lukas, Lopes Oliveira Gabriella, Neuzil Jiri (2022)

Event: Bioblast 2022

Our research has documented horizontal transfer of mitochondria in a mouse model of cancer from stroma to cancer cells with compromised oxidative phosphorylation (OXPHOS) in order to restore respiration. Functionally, the restoration of the ability to respire was attributed to the OXPHOS-linked activity of dihydroorotate dehydrogenase (DHODH), a mitochondrial enzyme catalysing the 4th reaction of the de novo pyrimidine synthesis. One biological event epitomized by high proliferation is liver regeneration after partial hepatectomy (PHx), with liver re-growth after 60% PHx in mouse in 5-6 days. Consistent with the notion that this process requires highly robust liver cell proliferation, we found that blocking the de novo pyrimidine synthesis prevents the regeneration process. Additionally, to support the massive requirement for proliferation, the liver switches from ammonia detoxification to diversion of this toxic metabolite into pathways supporting formations high level glutamate and glutamine, substrates of amino acids and nucleotides. Thus, to sustain the high level of proliferation in regenerating liver, metabolism switches to anabolic pathways, also making use of ammonia that would otherwise be converted into the waste product urea.


O2k-Network Lab: AU Queensland Neuzil J, CZ Prague Neuzil J


Affiliations

Endaya BB1, Le TDD1, Kucera L2, Lopes Oliveira G1,3, Neuzil J4
  1. Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic
  2. Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic
  3. University of Coimbra, Portugal
  4. Griffith University, Southport, Qld, Australia

Help


Labels: