Open AccessMetabolic determination of cell fate through selective inheritance of mitochondria
Author(s) -
Julia Döhla,
Emilia Kuuluvainen,
Nadja Gebert,
Ana Luísa Amaral,
Johanna Englund,
Swetha Gopalakrishnan,
Svetlana Konovalova,
Anni I. Nieminen,
Ella S Salminen,
Rubén Torregrosa Muñumer,
Kati J. Ahlqvist,
Yang Yang,
Hien Bui,
Timo Otonkoski,
Reijo Käkelä,
Ville Hietakangas,
Henna Tyynismaa,
Alessandro Ori,
Pekka Katajisto
Publication year - 2022
Publication title -
nature cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 11.38
H-Index - 369
eISSN - 1476-4679
pISSN - 1465-7392
DOI - 10.1038/s41556-021-00837-0
Subject(s) - mitochondrion , cell fate determination , oxidative phosphorylation , biology , microbiology and biotechnology , cell division , metabolism , pentose phosphate pathway , stem cell , cell , biochemistry , metabolic pathway , organelle , glycolysis , gene , transcription factor
Metabolic characteristics of adult stem cells are distinct from their differentiated progeny, and cellular metabolism is emerging as a potential driver of cell fate conversions 1-4 . How these metabolic features are established remains unclear. Here we identified inherited metabolism imposed by functionally distinct mitochondrial age-classes as a fate determinant in asymmetric division of epithelial stem-like cells. While chronologically old mitochondria support oxidative respiration, the electron transport chain of new organelles is proteomically immature and they respire less. After cell division, selectively segregated mitochondrial age-classes elicit a metabolic bias in progeny cells, with oxidative energy metabolism promoting differentiation in cells that inherit old mitochondria. Cells that inherit newly synthesized mitochondria with low levels of Rieske iron-sulfur polypeptide 1 have a higher pentose phosphate pathway activity, which promotes de novo purine biosynthesis and redox balance, and is required to maintain stemness during early fate determination after division. Our results demonstrate that fate decisions are susceptible to intrinsic metabolic bias imposed by selectively inherited mitochondria.