Each cell in an organism has a sensor¹ that measures the health of its "internal" environment. This "alarm" is found in the endoplasmic reticulum (ER内质网), which is able to sense cellular² stress and trigger either rescue responses or the death of the cell. A team from the Institute for Research in Biomedicine (IRB), in Barcelona, has discovered that the protein Mitofusin 2 (Mfn2) plays a crucial role in correctly measuring stress levels, and also makes sure the pathways of cell repair or cell death are effective. The researchers reveal some of the molecular³ mechanisms⁴ that connect Mfn2 to endoplasmic reticulum stress in the latest edition of the scientific journal, EMBO Journal, from the Nature Group, published by the European Molecular Biology Organization.

 

When the scientists removed Mfn2 from the cell under conditions of cell stress, the endoplasmic reticulum responded by over-activating the repair pathways. By doing so, it contradictorily⁵ functioned worse, reducing the capacity of cells to overcome the stress insult and promoting to a lesser⁶ degree apoptotic cell death. "When Mfn2 is removed, the cellular stress response pathways are completely disrupted," says Antonio Zorzano, coordinator⁷ of IRB's Molecular Medicine Programme and leader of the group "Heterogenic and polygenic diseases."

 

 

Mfn2 is a mitochondrial（线粒体的） protein whose deficiency is related to diabetes. In an earlier publication in Proceedings⁹ of the National Academy of Sciences (PNAS), Dr. Zorzano's research team demonstrated that without Mfn2, tissues become resistant¹⁰ to insulin, a characteristic of diabetes and the so-called metabolic¹¹ syndrome¹². In this study, they also observed that the cells had higher endoplasmic reticulum stress.

 

The current study investigates the relationship between mitochondria and the endoplasmic reticulum, and indicates that changes in mitochondria, caused by the loss of the Mfn2 protein, directly affect the endoplasmic reticulum function. "We have shown that Mfn2 is important for cell viability¹³ and has implications for numerous diseases, such as neurodegeration, cancer, cardiovascular disease, in addition to diabetes," says postdoctoral researcher Juan Pablo Muñoz, first author of the study.

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