• How our body controls inflammation durin

    From ScienceDaily@1:317/3 to All on Fri Feb 4 21:30:46 2022
    How our body controls inflammation during clean-up mechanisms of damaged
    cells

    Date:
    February 4, 2022
    Source:
    University of Cologne
    Summary:
    A research team has investigated in detail how messenger substances
    signal inflammation during the removal of damaged cells in the body.

    Using high-resolution microscopy methods, the researchers were able
    to show that two proteins interact dynamically with each other
    and thus determine whether a dying cell triggers an inflammatory
    reaction in the body.



    FULL STORY ==========================================================================
    A research team from Cologne and Osnabru"ck has investigated in detail
    how messenger substances signal inflammation during the removal of
    damaged cells in the body. Using high-resolution microscopy methods,
    the researchers were able to show that two proteins interact dynamically
    with each other and thus determine whether a dying cell triggers an inflammatory reaction in the body.


    ==========================================================================
    The study led by Professor Dr. Ana J. Garcia-Saez (CECAD -- Cluster
    of Excellence for Aging Research at the University of Cologne) and
    Junior Professor Dr. Katia Cosentino (CellNanOs -- Center for Cellular Nanoanalytics at the Osnabru"ck University) has been published in the
    journal Molecular Cell under the title 'The interplay between BAX and
    BAK tunes apoptotic pore growth to control mitochondrial DNA-mediated inflammation'.

    Normally, the body initiates apoptosis -- a form of programmed cell
    death -- to get rid of damaged cells. Knowledge of how exactly this
    clean-up mechanism functions at the level of the molecules involved can
    make a significant contribution to the therapy of diseases. In cancer,
    for example, the cells are not systematically removed from the body,
    but continue to live and spread.

    Radiotherapy treatment is routinely used to kill cancer cells, but it
    induces inflammation in the body. Research is being carried out worldwide
    to find out how cancer therapies cause inflammation and how treatments
    can be less harmful to the body.

    In this study, the research team from CECAD and CellNanOs focused on
    two proteins that are already known to be involved in cell death. BAX
    and BAK are the two proteins that regulate the cell death mechanism
    in mitochondria, the power-houses of the cell. Using high-resolution
    imaging techniques, the researchers were able to observe for the first
    time how dynamically BAX and BAK formed structures in mitochondria that influenced cell death and inflammation.

    Due to their great similarity, BAX and BAK have so far been referred to
    as twin proteins. That they differ systematically in their mechanism of
    action is a new finding of this study. The research team was able to show
    that BAK proteins organize into smaller structures more quickly than BAX,
    and that the two proteins influence each other.

    'We could clearly observe under the microscope how both proteins
    interacted with each other to form a pore in the mitochondrion, so that
    the mitochondrial DNA exited through the pore to trigger inflammation,' explained Andreas Jenner of the University of Cologne. This dynamic
    interplay of BAK and BAX proteins was previously unknown, and it
    regulates the formation of the pore and thus the amount of mitochondrial
    DNA released. This, in turn, determines whether an inflammatory response
    is triggered in the body.

    'The relative availability of BAX and BAK proteins in cells determines the growth of the pore and the rate at which mitochondrial DNA is released.

    Possibly, our findings open up new perspectives to control inflammation
    during cancer treatments,' explained Katia Cosentino of the Osnabru"ck University.

    'Our results highlight how BAX and BAK contribute to cell death in
    different ways and suggest that these two proteins should be well
    balanced in therapeutic cancer treatments,' said Ana J. Garcia-Saez of
    the University of Cologne.

    However, such therapy does not yet exist. For now, further investigation
    is needed to determine whether additional molecules contribute to the
    dynamics of BAX and BAK pore formation and regulate pore growth and size.

    Work for the study began at the IFIB (Interfaculty Institute of
    Biochemistry) in Tu"bingen and was completed at the CECAD Research Center, Institute of Genetics, in the Garcia-Saez laboratory in Cologne and
    at the Center for Cellular Nanoanalytics (CellNanOs) at the Osnabru"ck University.

    ========================================================================== Story Source: Materials provided by University_of_Cologne. Note: Content
    may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Katia Cosentino, Vanessa Hertlein, Andreas Jenner, Timo Dellmann,
    Milos
    Gojkovic, Aida Pen~a-Blanco, Shashank Dadsena, Noel Wajngarten,
    John S.H.

    Danial, Jervis Vermal Thevathasan, Markus Mund, Jonas Ries, Ana J.

    Garcia-Saez. The interplay between BAX and BAK tunes apoptotic pore
    growth to control mitochondrial-DNA-mediated inflammation. Molecular
    Cell, 2022; DOI: 10.1016/j.molcel.2022.01.008 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/02/220204113438.htm

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