Scientists from the Weizmann Institute measured the levels of lipids in the cell nuclei and mitochondria at different times of the day, and discovered that about a third of the lipids measured show a daily change in the organelles. The findings may indicate the importance of time in basic life processes.
Whether we are early risers or night owls, our bodies are controlled by internal clocks ("circadian clocks"), which dictate a daily routine of about 24 hours. These watches are the focus of research in the laboratory of Dr. Gad Asher, from the Department of Biomolecular Sciences at the Weizmann Institute of Science. The biological clocks work in every organism that is sensitive to light, and surprisingly, a few years ago it was discovered that they "tick" in every cell in the body, even when the cells are separated from the body. The discovery of independent cellular clocks ignited the research question of research student Rona Aviram, under the guidance of Dr. Asher: Are there circadian clocks also in intracellular organelles? This is of great importance from an evolutionary point of view, since the answer may indicate a hierarchy in the development of the clock: whether at the level of the molecules, the cell, the organ, or the entire organism. Time, therefore, is important in the organization and coordination of various biological processes in animals, starting with their basic biochemistry.
In order to answer the question, are there circadian clocks also in intracellular organelles, one must face the question "How can time or clock activity be measured?" For example, in the 18th century, the botanist Carolus Linnaeus came up with the "Horologium Floria", the "Flower Clock", in which each hour of the day is represented by the opening of petals in different flowers, an activity controlled by their internal clock. "How can you see the passing of time? How do you know if there is a clock, and if so - what time is it?" Aviram asks, and explains: "Many studies use changes in gene expression, because many genes are expressed at different levels during the day, or a change in the activity level of some protein. To examine time in the organs, you need to find a common denominator to compare them. Therefore, we chose to examine the daily levels of lipid-type metabolites, i.e. fat molecules. The lipids are found both in the cell nucleus and in the mitochondria, and they are particularly interesting because they also serve as a selective mediator between the organelle and its environment and are also active in many cellular processes."
The scientists measured the levels of different lipids around the clock in the cell nuclei and mitochondria isolated from the livers of mice that were given unlimited access to food. Out of all the measurements, they checked the results of lipids that reach one peak during 24 hours, that is, those that exhibit circadian (daily) behavior. The two discoveries that emerged from the results are these: there are very large changes in lipids during the day - 30% of the lipids measured show a daily change in the organelles, and the circadian peaks are reversed between the organelles. In the cell nucleus, most of these lipids accumulated mainly at the beginning of the day, during the light hours, while in the mitochondria the opposite behavior was recorded, with most of the lipids accumulating at the beginning of the night, during the dark hours. Thus the fats became a kind of hands of a clock, since their presence at peak levels indicates the time in that organ.
The researchers wanted to check the effect of the time of eating on the daily rhythm of the lipids in the organs. In a condition of unlimited feeding, mice eat 70% of the food during their active hours, at night. Therefore, at this stage, the researchers limited the feeding to night only, and the profile of the lipids was reversed - in the nucleus, the peak of lipids shifted from the beginning of the day to the beginning of the night, and in the mitochondria, it shifted from the beginning of the night to the beginning of the day. Following this phenomenon, the scientists hypothesized that there is a mechanism that links the activity in the organelles, and maintains the coupling of the inverse ratio between the lipid peaks.
In a test carried out in mutant mice whose circadian clock is inactive and they were fed at night, no significant peak of lipids was found in any of the organelles; There was a scattering of them during the day. The researchers hypothesize that the circadian clock may mediate the connection between the organelles in this aspect. Future studies may answer the question, whether the rhythmicity observed in the various organs originates from a clock that is present and operates in each of the organelles, or whether it is the result of one central clock that uniquely affects each of the organelles.
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34% of the lipids measured in the cell nucleus and 31% of the lipids measured in the mitochondria accumulated at a typical rate, at different times in the different organelles.
