Biological complexity: mitochondrial splitting, repair (Introduction)

by David Turell , Thursday, May 06, 2021, 15:31 (1297 days ago) @ David Turell

Two different systems for simple cell division and removing damaged parts:

https://www.nature.com/articles/d41586-021-01173-x?WT.ec_id=NATURE-202105&sap-outbo...

"During mitophagy, damaged portions of mitochondria separate from healthy portions through mitochondrial division6. However, damage is not the only reason for mitochondrial division. It also occurs during cell growth and cell division. In this scenario, the new cellular property generated by cell division is furnished using mitochondria generated by division. In contrast to damage-associated division, mitochondrial division during cell growth is a sign that times are good.

"It stands to reason that different mechanisms control mitochondrial division for mitophagy and for cell growth. Although there have been hints of specific types of division, clear evidence has been lacking until now. The protein DRP1 is required for the vast majority of cases of mitochondrial division6. DRP1 can be activated in different ways to drive such division in mammals. These include: interaction with mitochondrial DRP1 receptors (MFF, MID49, MID51 and FIS1); DRP1 modification (post-translational alterations); interaction with the actin cytoskeleton (filaments of actin protein) or the mitochondrial lipid cardiolipin; and contact with various organelles, including the endoplasmic reticulum (ER), lysosomes and the Golgi (in the form of Golgi-derived vesicles). It has been unclear whether these factors contribute to a single division pathway or to different pathways.

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"The authors demonstrate that peripheral and midzone divisions have substantially different properties. Midzone division occurs in organelles with hallmarks of healthy mitochondria — they do not display signs of abnormalities, such as a reduction of membrane polarization or a change in the level of reactive oxygen species (ROS). By contrast, peripheral division occurs when the tip of the organelle has developed a decrease in membrane potential and an increase in ROS, with a noticeable lack of these alterations in the other portion of the organelle. In addition, this smaller product of a peripheral division often lacks replicating DNA — which is a sign of an unhealthy mitochondrion. (my bold)

"These findings suggest that peripheral division occurs when mitochondria are damaged, and is a precursor to mitophagy. Indeed, the authors report that peripheral divisions increased on exposure to various cellular stresses, and were associated with the accumulation of markers of mitophagy. By contrast, midzone division increased after stimulation of cell proliferation.

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"Kleele and colleagues’ careful work is valuable, because it clearly demonstrates that there is more than one type of mitochondrial division, thus enabling a more nuanced analysis of division factors based on the reason for division. Moreover, this work is a reminder that we need to walk before we can run when trying to map complicated biological processes such as mitophagy. Otherwise, our understanding of them might be hampered by an incomplete grasp of the earlier processes that lead up to them."

Comment: Exciting new research into the mysterious mitochondria in normal cell division and in controlling damage. Mitochondria supply energy by the process of oxidation, handling dangerous reactive oxygen species (ROS). As in a fire, oxygen burns. The deeper we go the more complex it gets in the creators designs. This is a review paper on early research and much of it asks probing questions.