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Breaking point: mechanical stress helps NINJ1 protein to rupture membranes

The protein NINJ1 enables cells to break open during certain types of cell death. Modulation of physical forces on the membrane reveals how NINJ1 acts.
By
  1. Ishan Deshpande

    1. Ishan Deshpande is in the Department of Physiological Chemistry, Genentech, South San Francisco, California 94080, USA.

  2. Vishva M. Dixit

    1. Vishva M. Dixit is in the Department of Physiological Chemistry, Genentech, South San Francisco, California 94080, USA.

The cell membrane is more than just a passive barrier — it’s also a front-line defence system that is constantly challenged by mechanical forces, such as muscle stretch. Although cells have repair systems to maintain their integrity, sufficient physical stress can tear the outer membrane and release a cell’s contents, including inflammatory molecules. This type of catastrophic rupture, which also occurs in certain types of infection-associated cell death, is triggered1 by a membrane protein called NINJ1. Does NINJ1 respond to mechanical stress, and if so, what determines its activation threshold? Writing in Nature, Zhu et al.2 provide compelling answers to these fundamental questions.

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doi: https://doi.org/10.1038/d41586-025-02130-8

References

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Competing Interests

The authors declare no competing interests.

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