The house where a cell lives has four rooms: mitochondria, the nucleus, the cytosol, and the plasma membrane. Until now we could only see that a fire had lit up somewhere, without knowing which room it was in. Now we have four windows, and each one shows its own part of the house. The fire in this house is hydrogen peroxide, a small signaling molecule that oxidizes proteins the way rust eats into iron. But rust destroys, while peroxide acts more subtly: it switches proteins on or off for a short time, passing along a signal.
To see this fire in every room, scientists engineered the HyPer7 sensor into Drosophila. This protein glows differently when peroxide appears nearby. The sensor was sent to the right room using signal sequences: COX8 for mitochondria, three copies of NLS for the nucleus, NES for the cytosol, and myristoylation for the plasma membrane. That is how four fly lines came about, each with its own window. The sensor turned out to be so sensitive that it can register oxidation from a single peroxide molecule that has diffused into the reaction zone.
Testing in living tissues produced unexpected pictures. In the ovaries, mitochondria flared and faded within six minutes after peroxide was added, revealing the work of antioxidant systems. In wing imaginal discs, the buds of the future wing, the nuclear sensor became oxidized in the peripodial membrane, while the membrane sensor stayed reduced along the boundaries where cells divide. In embryos, the plasma membrane oxidized brightly in yolk granules and at the leading edge during dorsal closure, when the edges of the embryo come together like a zipper closing. The nuclear sensor lit up in the salivary glands at stage 14.
These observations show that hydrogen peroxide does not simply spill across the cell, but works differently in each room. In old flies, the cytosolic sensor in gut cells was more oxidized than in young ones, meaning that oxidative stress accumulates in this room with age. Previously we could not see exactly where this chemical work was happening, but now we can follow it in real time. Four windows are open, and the fire in each room is visible separately. It is like watching a house where dinner is cooking in one room, someone is reading a book in another, people are asleep in a third, and a signal lamp is burning in the fourth.
The HyPer7 sensor is so sensitive that it can register oxidation from a single molecule of hydrogen peroxide that has diffused into the reaction zone. At the same time, it is reduced by the thioredoxin system, so it actually reports not just the presence of peroxide but the balance between oxidation and reduction.
The idea of seeing invisible signaling molecules inside a living cell echoes the concept of 'inner vision' from Stanisław Lem's novel Solaris, where an ocean-mind communicates through subtle chemical signals. Here, scientists gain the ability to literally watch the chemical language of cells in action.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.