Maintaining the fasting/fusion detour a little longer: out walking today I wondered why do stem cells divide symmetrically under mitochondrial fusion? The has not been discussed, as far as I am aware.
It seemed quite obvious. Many of us know from experience the regenerative properties of fasting; indeed Longo observed that white blood cell counts drop off during fasting, as old cells are recycled for energy, but spike on refeeding (above pre-fasting levels) - the cause? Stem cells. To borrow from Cynthia Kenyon, we clearly possess this latent capacity to live longer under CR (and or possibly fasting), so fasting would of course represent something of a short-term gain if stem-cell pools were depleted during tough times, we'd wind up burning twice as bright but half as long, so symmetric differentiation would allow the body to service its need for rejuvenation during lean times but also retain a priori levels of stem cells. Additionally, it would make a lot of evolutionary sense for mitochondria to fuse during fasting since, depleted of energy, a fusion boost would represent a critical advantage. The mitochondrial fused state then presumably signals symmetric differentiation.
If true, then it shouldn't be a problem to retain a fused state for a few weeks at a time (unless say there is some periodic forced fission during fasting to maintain the plasticity mentioned important in the article a few posts back). Certainly, there are peaks and troughs in energy-levels during extended fasts.
I addressed the fusion/self-renewal question with a reference in the first post, but here is more lengthy excerpt--
We now uncover that the state of an organelle, namely mitochondria, has the capacity to coordinate self-renewal versus differentiation of stem cells. Mitochondria are dynamic organelles that undergo morphological changes through fission and fusion. Although major changes in mitochondrial structure have been generally attributed as a cellular response to stress, we now present evidence that mitochondrial dynamics can act as a functional regulatory factor, beyond ATP generation, in the context of physiological and developmental processes. In fact, mitochondrial dynamics serves as a regulatory point for the coordination of a nuclear developmental program in NSCs, by dictating the cellular redox state.ROS have been historically viewed as toxic byproducts of cellular redox reactions, but they have recently gained a more positive perspective as physiological signaling molecules (Sena and Chandel, 2012). Work in the stem cell field has proposed a role for ROS in the differentiation of stem cells, but the mechanisms are not fully understood. Furthermore, it is currently unknown as to how ROS levels are modified in stem cells. Here, we identify mitochondrial dynamics as the mechanism by which physiological levels of ROS can be fine-tuned, and we establish a fundamental role for ROS as physiological signaling molecules that modify the nuclear transcriptional profile of stem cells through an NRF2-mediated mitochondrial to nuclear retrograde pathway. In essence, we present a model whereby changes in mitochondrial structure direct the fate of stem cells. In this model, elongated mitochondria in NSCs maintain low ROS levels and promote self-renewal, while a transition of mitochondria to a more fragmented state results in a modest increase in ROS levels, thereby inducing the expression of genes that inhibit self-renewal (Botch) and promote commitment and differentiation.
