2023-11-01 07:00:15
Rainbow trout head. HUGO WILLOCX / BIOSPHOTO
Living cells can devour themselves. This process of autophagy (from the Greek “eating oneself”) allows them not only to recycle and renew their own constituents, but also to survive stress. The Japanese Yoshinori Ohsumi, who demonstrated the workings of this mechanism in the 1990s, received the Nobel Prize in 2016.
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The cells, basically, invented here the selective sorting and recycling of their waste. In practice, they implement several of these virtuous circuits. In the one that interests us, “garbage trucks” (protein chaperones) first recognize the proteins to be degraded – those which have become useless, defective or toxic. This is the first step. Then, these trucks collect them and transport them to the cell’s waste processing centers: the lysosomes. There, these expired proteins will be broken down by enzymes. Their elementary building blocks (amino acids) can then be reused to make a brand new stock of functional proteins.
It was long believed that only mammalian and bird cells were capable of performing autophagy. But this dogma was revised in 2020, when a team from the National Research Institute for Agriculture, Food and the Environment (Inrae) and the University of Pau and the Pays de l’Adour, discovered this ability in a small Asian fish, the medaka.
“Trout, a natural model of glucose intolerance”
Trout also uses this self-digestion process, this team shows today. “Autophagy probably exists in all fish. It is therefore a much older phenomenon than we thought.relieves Ivan Seiliezwho coordinated this work published on October 5 in the journal Autophagy.
Importantly, this mechanism helps cells resist high concentrations of glucose. “Like other carnivorous fish, trout is a natural model of glucose intolerance, this cellular state present in humans with prediabetes”, explains Emilio Vélez, first author of the study. Clearly, trout, which feed mainly on proteins, are not equipped to cope with high quantities of sugar.
What happens in the cells of this salmonid, subjected to high levels of glucose? The researchers monitored the process using a fluorescent probe coupled to the “tag” (a short sequence of amino acids) that marks the proteins to be degraded. And here is the cascade of events they traced. Excess sugar first leads to a dysfunction of the mitochondria, these energy factories of the cells. This stress causes the oxidation of many proteins; a key gene (Lamp2A) then activates and triggers this form of autophagy. Eventually, the oxidized proteins will be degraded in lysosomes.
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