Biological complexity: mitochondrial cell differentiation (Introduction)

by David Turell , Sunday, March 24, 2019, 00:23 (1854 days ago) @ David Turell

Mitochondria actually have control over several types of cell differentiation:

https://www.quantamagazine.org/shape-shifting-mitochondria-direct-stem-cells-fate-20190...

"One crucial role that has emerged is in promoting the differentiation of various types of stem cell, including those for blood and fat cells — and, most recently, for neurons.

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"In 2016, Slack, Khacho and their colleagues reported the first evidence that mitochondrial shape-shifting is a key regulator of neural stem cell fate, the decision to self-renew or differentiate. By deleting genes that encoded key proteins for the fusion and fission machinery in mice, they discovered that a deficiency in fusion proteins reduced neural stem cells’ capacity to replenish themselves and encouraged the cells to become neurons. A loss of fission proteins, on the other hand, stimulated the stem cells to self-renew.

"Their work showed that changes in the shape and architecture of mitochondria are among the earliest, most “upstream” signals to determine which way neural stem cells will go.

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"The real significance of Slack and Khacho’s work in neural stem cells might be that the mitochondria’s role in neurogenesis relates to something more dynamic than shape alone. According to Khacho, it’s likely that what matters isn’t the organelles’ form in a cell at a given moment, but rather their ability to morph through fission and fusion. Fission and fusion are happening all the time, and so far, scientists have only been looking at snapshots of this process. “Perhaps it’s the plasticity, the ability to change,” Khacho said. “That’s the important thing.”

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"Findings from Slack, Khacho and their colleagues suggest that changes in mitochondrial structure could modify the amount of ROS in cells. They’ve shown that fission and fusion can control levels of ROS, [reactive oxygen species] which can in turn regulate the decisions of stem cells to proliferate or differentiate.

“'What they found is something interesting,” Chandel said. “The same ROS signaling that we’ve been talking about for 20 years happens in neurons, and mitochondrial dynamics can control that.”

"But ROS is probably only part of the answer. Mitochondria can communicate with the cell in many ways, such as through the generation of other metabolites, the release and uptake of calcium, and changes in membrane potential. “Any signaling molecules that result from metabolic changes — and there are many, many molecules — could be important,” Slack said.

"Moreover, it’s unlikely that the same mitochondrial signals control the fate of different stem cell types. “We know that [mitochondria] participate in a number of differentiation processes,” said Luca Scorrano, a biochemist at the University of Padua in Italy. But “as soon as we look into the specificity of the mitochondrial participation … we see that the signaling cascades which are regulated by mitochondrial dynamics are not necessarily the same.'”

Comment: Mitochondria do much more than produce energy. More complex than realized as each layer of the onion is peeled away.