Can limiting protein intake (or other selective nutrient depletion) induce autophagy?

Can limiting protein intake (or other selective nutrient depletion) induce autophagy?


[Rhonda]:…my next question was I know that
if you take cultured cells in a dish and you just…you’re doing some, you know, specific
nutrient withdraw, you withdraw amino acids when you withdraw glucose, or you withdraw
glutamine, you can induce autophagy. But in the whole organism, for example, in
mice and in humans, ultimately, you know, can you just limit your protein intake for
a week and induce autophagy even in the presence of a normally caloric diet where you’re still
getting enough energy. [Dr. Kroemer]: That’s a good question. We have never tested to selective completion
of one or the other nutrient, I suppose that this would work, because protein depletion
may affect a newer endocrine factors like insulin growth factor that, at the end, will,
due to its depletion, decrease the transport of glucose into the cells. And hence, stimulate autophagy. But it has not been tested thoroughly in mice. What we usually do is we starve mice and sometimes
human volunteers completely from any kind of caloric uptake, and in this case, we do
see, at the whole body level, that in all major cell types, perhaps with the exception
of the brain that is somehow buffered against this effect, protein deacetylation occurs
mostly in the cytoplasm. [Rhonda]: And that’s a biomarker of autophagy,
you would say? [Dr. Kroemer]: Well, it’s too early to say
that it is a surrogate or proxy of autophagy. So far, we have not been able to dissociate
the two phenomenon, autophagy and protein deacetylation, in the response to nutrients. However, when you induce autophagy by pharmacological
tricks, such as cell permeable peptides that dissociates an inhibitory interaction between
a Golgi protein and Beclin 1. You can induce autophagy without that protein,
deacetylation would occur before. And similarly, when you give chemical inhibitors
of mTOR like rapamycin or the rapalogs, there’s also no protein deacetylation. So, you can induce autophagy without protein
deacetylation which means that the proxy would be imperfect. So we do have a system to measure autophagy
which is relatively easy to be used in experimental systems which is the study of the redistribution
of LC3 and other members of the same family that are usually diffusely distributed all
over the cell, mostly in the cytosol, and then we’ll aggregate or redistribute towards
autophagosomes and autolysosomes. So they acquire a punctate distribution small
dots in the cytoplasm and these dots can be seen by fluorescence microscopy if LC3 is
labeled by immunofluorescence or when it is fused with green fluorescent protein or similar
biosensors.

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4 thoughts on “Can limiting protein intake (or other selective nutrient depletion) induce autophagy?

  1. Watch the full episode:
    https://www.youtube.com/watch?v=Gm626MgpveI&t=6s

    FoundMyFitness episode page:
    https://www.foundmyfitness.com/episodes/guido-kroemer

    More clips from this guest:
    https://www.youtube.com/playlist?list=PLrGxo-5Uw8gJJa4R_-vlojMyq0GJK6xkn

  2. I have a feeling that fasting or anything that has a similar effect could help with autoimmune or digestive issues.

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