N-terminal cleavage of cyclophilin D boosts its ability to bind F-ATP synthase.

Cyclophilin (CyP) D is a regulator of the mitochondrial F-ATP synthase. Here we report the discovery of a form of CyPD lacking the first 10 (mouse) or 13 (human) N-terminal residues (ΔN-CyPD), a protein region with species-specific features. NMR studies on recombinant human full-length CyPD (FL-CyPD) and ΔN-CyPD form revealed that the N-terminus is highly flexible, in contrast with the rigid globular part.

Cyclophilin D in Mitochondrial Dysfunction: A Key Player in Neurodegeneration?

Mitochondrial dysfunction plays a pivotal role in numerous complex diseases. Understanding the molecular mechanisms by which the "powerhouse of the cell" turns into the "factory of death" is an exciting yet challenging task that can unveil new therapeutic targets. The mitochondrial matrix protein CyPD is a peptidylprolyl - isomerase involved in the regulation of the permeability transition pore (mPTP).

Mitochondrial F-ATP Synthase and Its Transition into an Energy-Dissipating Molecular Machine.

The mitochondrial F-ATP synthase is the principal energy-conserving nanomotor of cells that harnesses the proton motive force generated by the respiratory chain to make ATP from ADP and phosphate in a process known as oxidative phosphorylation. In the energy-converting membranes, F-ATP synthase is a multisubunit complex organized into a membrane-extrinsic F sector and a membrane-intrinsic F domain, linked by central and peripheral stalks. Due to its essential role in the cellular metabolism, malfunction of F-ATP synthase has been associated with a variety of pathological conditions, and the enzyme is now considered as a promising drug target for multiple disease conditions and for the regulation of energy metabolism.