Age-dependent asymmetric apportioning of mitochondria during division determines cell fate
Julia Döhla1,2, Ana Amaral1, Ella Salminen2, Johanna I Englund2, Swetha Gopalakrishnan2, Nadia Gebert3, Alessandro Ori3, Pekka Katajisto1,2*
1Institute of Biotechnology, HiLIFE, University of Helsinki, Finland; 2Department of Biosciences and Nutrition, Karolinska Institute, Sweden; Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany
*Corresponding Author (email@example.com)
The maintenance of tissue renewal requires a balance between self-renewal and differentiation that can be achieved by asymmetric cell divisions. To ensure homeostasis throughout the lifespan, asymmetric divisions must be tightly regulated but it remains unknown which early decision mechanisms determine the fate of adult stem cells during such divisions. We have discovered age-dependent apportioning of mitochondria during asymmetric divisions as a potential mechanism guiding fates of the daughter cells. Stem-like human mammary epithelial cells (HMECs)1 apportion old mitochondria selectively to the differentiating daughter cell, while progeny omitting old mitochondria retains stem-like properties2. In this work we have characterised how the functional characteristics of the inherited mitochondria determine metabolic and functional properties of the daughter cells. Asymmetric apportioning of old mitochondria may therefore functionally contribute to the maintenance of a functional stem cell pool, and have important implications for the regenerative capacity of stem cells.
1. Chaffer, C. L. et al. Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state. Proc. Natl. Acad. Sci. U. S. A. 108, 7950-7955 (2011).
2. Katajisto, P. et al. Asymmetric apportioning of aged mitochondria between daughter cells is required for stemness. 348(6232): 340-3 (2015).