Post-translational modifications of the mitochondrial F1FO-ATPase

Biochimica et Biophysica Acta - General Subjects

5 years ago

Post-translational modifications of the mitochondrial F1FO-ATPase

The mitochondrial F1FO-ATPase has the main role in synthesizing most of ATP, thus providing energy to living cells, but it also works in reverse and hydrolyzes ATP, depending on the transmembrane electrochemical gradient. Within the same complex the vital role of the enzyme of life coexists with that of molecular switch to trigger programmed cell death. The two-faced vital/lethal role makes the enzyme complex an intriguing biochemical target to fight pathogens resistant to traditional therapies and diseases linked to mitochondrial dysfunctions. A variety of post-translational modifications (PTMs) of selected F1FO-ATPase aminoacids have been reported to affect the enzyme function.

Scope of review

By reviewing the known PTMs of aminoacid side chains of both F1 and FO sectors according to the most recent advances, the main aim is to highlight how local chemical changes may constitute the molecular key leading to pathological or physiological events.

Major conclusions

PTMs represent the chemical tool to modulate the F1FO-ATPase activity in response to different stimuli. Some PTMs are required to ensure the enzyme catalysis or, conversely, to inactivate the enzyme function. Each covalent modification of the F1FO-ATPase, which occur in response to local changes, is the result of a selective molecular mechanism which, by translating a chemical modification into a biochemical effect, guarantees the enzyme tuning under changing conditions.

General significance

Once highlighted how the molecular mechanism works, some PTMs may be exploited to modulate the effect of drugs targeting the enzyme complex or constitute promising tools for F1FO-ATPase-targeted therapeutic strategies.

Publisher URL: www.sciencedirect.com/science

DOI: S0304416517302520