• Cell biology: How mitochondria report st

    From ScienceDaily@1:317/3 to All on Thu Apr 7 22:30:42 2022
    Cell biology: How mitochondria report stress

    Date:
    April 7, 2022
    Source:
    Ludwig-Maximilians-Universita"t Mu"nchen
    Summary:
    Researchers have discovered the mechanism by which the protein DELE1
    detects organelle stress. This offers a possible new approach for
    treating neurodegenerative diseases.



    FULL STORY ==========================================================================
    LMU researchers have discovered the mechanism by which the protein DELE1 detects organelle stress. This offers a possible new approach for treating neurodegenerative diseases.


    ========================================================================== Researchers have long posited a link between dysfunctions in mitochondria, little organelles in the interior of cells, and the aging process and age- related illnesses, such as Alzheimer's disease. "Many such illnesses
    cannot be cured -- partly because we don't yet understand fundamental mechanisms," says Professor Lucas Jae from LMU's Gene Center Munich.

    Frequently, the mitochondrial dysfunction is triggered by various forms of stress -- this much is known. Stress can come from the cell or originate
    in the mitochondrion itself, such as through reactive oxygen species,
    which occur during cellular respiration. Although they have their
    own genome, mitochondria are incapable of responding independently to
    stress. "This means that disturbances must be reported to the rest of
    the cell," explains Dr. Evelyn Fessler from the Gene Center Munich.

    In Nature Communications, Fessler and Jae, together with Luisa Krumwiede, describe a mechanism whereby a special protein in humans, DELE1, detects various kinds of stress while being imported into mitochondria and reports
    them to the cell. This can lead to different responses, such as repairs
    or induced cell death.

    Known molecule, unknown mechanism Two years ago, Jae's team explored
    the question as to how mitochondrial stress is actually reported to the
    cell. The researchers found a new signaling pathway consisting of the
    proteins OMA1, DELE1, and HRI, which looks after such tasks.

    "So we knew which factors recognize mitochondrial stress, but we didn't understand key aspects," recalls Jae. "How does the DELE1 signal travel
    from the mitochondrion into the cytoplasm of the cell? And how can
    DELE1, as an individual protein, detect the many different types of
    stress?" Now the researchers have found answers. DELE1 is continuously imported into the mitochondria and processed by proteases. Deep inside
    the mitochondria, DELE1 is then quickly degraded. As such, there are
    molecules constantly passing through the outer and inner membranes of mitochondria in order to be imported.

    Mitochondrial stress causes this importing process to fail. New
    DELE1 molecules are arrested on their way into the mitochondria and,
    depending on the source of the disturbance, are either cut by OMA1 or
    remain uncleaved outside the organelles. In any case, the portion of
    the DELE1 protein that possesses the signaling effect is unmasked in the cytosol. "All the different types of stress lead to one of the sub-steps involved in the importing and processing of DELE1 coming to a halt,"
    summarizes Jae. This is how mitochondrial stress is detected.

    DELE1 also recognizes dysfunctions in the mitochondrial enzymes PITRM1
    and MPP.

    In neurodegenerative diseases, these enzymes are mutated. "Specifically
    in connection with such defects, we have observed that it's important for cellular survival for DELE1 to detect the problem and inform the cell,"
    notes Jae.

    What happens next? "Now that we understand the mechanism, we can
    investigate many different scenarios," reports Fessler. The researchers
    want to discover how the decision is made as to whether a cell enters a
    repair phase due to a stress response or goes into programmed cell death, because otherwise it would present a danger. They also hope to be able
    to modulate the signaling pathway such that it favors cellular survival
    in times of mitochondrial stress: a possible approach for treating neurodegenerative diseases.


    ========================================================================== Story Source: Materials provided by
    Ludwig-Maximilians-Universita"t_Mu"nchen. Note: Content may be edited
    for style and length.


    ========================================================================== Journal Reference:
    1. Evelyn Fessler, Luisa Krumwiede, Lucas T. Jae. DELE1 tracks
    perturbed
    protein import and processing in human mitochondria. Nature
    Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-29479-y ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/04/220407141936.htm

    --- up 5 weeks, 3 days, 10 hours, 50 minutes
    * Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)