Picture: Clusters of long-lived mitochondria in neurons
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Older mitochondria (black arrow, maroon) and younger mitochondria (yellow arrow, cyan) show age mosaic (differential aging) between brain mitochondria
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Mitochondria are called the cell's power station, which produces energy and fuels the functions of our cells
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Now, scientists at the Salk Institute and the University of California San Diego (UCSD) have further studied how mitochondria are maintained in non-dividing cells (such as neurons).
The ultimate goal is Better understand how to prevent or treat age-related diseases
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Researchers have discovered that many proteins in mitochondria have a much longer lifespan than expected, and this stability may protect them from damage
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These findings were published in the journal Developmental Cell on October 28, 2021
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Martin Hetzer, senior author of the paper and senior vice president and chief scientific officer of Salk, said: "For a long time, people have been concerned about how specific cells in various tissues are maintained throughout their life cycles.
This question is very interesting
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" "One thing we want to understand is how a biological system composed of many dynamic components, such as proteins and biomolecules, can remain stable for a century in such a long-lived person
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The Hetzer laboratory uses genetic methods and advanced imaging techniques to study how tissue is maintained and repaired throughout its life cycle
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In a study published in 2012, his team looked at specific surface proteins in the nuclei of rodent brain cells
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They found that some of these proteins have a very long lifespan, in some cases even as old as the animal itself
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Based on previous work, Salk's Hetzer team and UCSD colleagues collaborated to conduct a more in-depth study of mitochondria in mouse brain cells
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They chose mitochondria because, like the nucleus, it is important that these organelles (cell structures) remain stable in order to maintain normal cell functions
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Like the nucleus, mitochondria also contain genetic material
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Hetzer said it makes sense to build a stable structure around mitochondria to protect their DNA
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In the mitochondria, the researchers decided to focus on the protein that is part of the electron transport chain, which is essential for the main function of the mitochondria to generate energy
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Researchers label these proteins with stable but unusual isotopes, which degrade over time
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This technique is similar to carbon dating, which is used by archaeologists to determine the age of materials of organisms that once existed
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"We were surprised to find that some mitochondrial proteins are still very stable and turn much slower than most proteins," said first author Shefali Krishna (Shefali Krishna), a worker in Heizer's laboratory.
Personnel
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To further understand why these long-lived mitochondrial proteins can survive for so long, they studied what happens if the protein's mRNA is exhausted, which contains the instructions to make more protein
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Krishna explained that the research team found that even if the mRNA is removed, these proteins remain in the cell for a long time and can maintain mitochondrial function
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This is in contrast to the mRNA removal of short-lived proteins, which are quickly depleted
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"Synthesizing new proteins is very energy intensive, so from the perspective of energy conservation, it makes sense to have long-lived proteins," Hetzer said
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"In addition, whenever you have to replace something, you introduce the risk of error, so keeping the protein can provide some protection against this
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"I like to use a car as an analogy; it has some parts that need to be replaced frequently, such as oil and tires, and some parts that take a long time to use, such as the engine
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" "In fact, the life of the engine often determines the life of the car.
, We hope that the battery’s engine can be used for as long as possible
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"This work provides another powerful example of how to study the lifespan of different cell components and organelles through the application of new high-resolution imaging techniques," co-author and UCSD professor Mark Ellisman (Mark Ellisman) Say
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The research team plans to continue to study these long-lived proteins in mitochondria to further clarify the role of mitochondria in aging diseases
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Original search:
10.
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devcel.
2021.
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