Research Paper Volume 8, Issue 7 pp 1330—1349

Mitophagy-driven mitochondrial rejuvenation regulates stem cell fate

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Figure 9. Mitophagy-regulated nuclear reprogramming of somatic cells into pluripotent stem cells. Mitophagy is part of the roadmap during nuclear reprogramming of somatic cells to pluripotency and, as such, its blockade is sufficient to dramatically alter the speed and efficiency of iPSC reprogramming by “elevating” the “reprogramming barriers” of the epigenetic landscape and decreasing the size of the stem cell state basin of attraction, which results in the deceleration (i.e., lower efficiency and slower kinetics) of the nuclear reprogramming process. This conceptual figure represent cells stabilized in an initial non-pluripotent, somatic attractor and how nuclear reprogramming can make cells exceed the “reprogramming barriers”, represented as a wall of interlocking bricks, easier or harder in the presence or absence of PINK1-dependent mitophagy, respectively, and fall down in a final attractor of fully reprogrammed, induced pluripotent stem cell states. The cellular reprogramming process is presented as a colored line from the initial to the final cellular state.