A salvage pathway in mitochondria to repair itself

A salvage pathway in mitochondria to repair itself

An energy supply to the cell that is disturbed by damage can protect itself from loss of function and repair it in a kind of workshop mode.  The findings were published in Nature Communications under the title “A salvage pathway maintains highly functional respiratory complex I”.

Mitochondria, the energy power plants that are inherent in every cell. Mitochondria perform very basic processes such as constantly supplying the cell with energy. The power plant machine in the mitochondria consists of five components, the so-called complexes I - V. In the end, the food we eat is converted into usable energy. If the cellular energy supply is no longer guaranteed due to disturbances in signal processes, this has serious consequences for the entire organism and diseases.

"In our most recent work, we discovered an escape route that cells can use to repair faults in a particularly sensitive part of Complex I," said the senior author. "Repairing something is a far more resource-efficient self-help mechanism compared to the effort that would be to completely destroy and rebuild this entire component."

The specific escape route identified by the authors also acts like a safety valve for the cell. If the escape route becomes active, the component that has lost its function quickly switches to a shutdown mode and comes “to the workshop”. In this way, the cells directly prevent harmful reactive oxygen species from being produced and released in the power plant machine. The senior author: “So far, very little is known about how this machine is maintained and regulated. Our results shed light on this process and allow us to explore other therapeutic options.”

The authors report that the NADH-oxidizing N-module of ComplexI (CI) is turned over at a higher rate and largely independently of the rest of the complex by mitochondrial matrix protease ClpXP, which selectively removes and degrades damaged subunits. The observed mechanism seems to be a safeguard against the accumulation of dysfunctional CI arising from the inactivation of the N-module subunits due to attrition caused by its constant activity under physiological conditions.

This CI salvage pathway maintains highly functional CI through a favorable mechanism that demands much lower energetic cost than de novo synthesis and reassembly of the entire CI.