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Review
. 2020 Jun 17:11:595.
doi: 10.3389/fphys.2020.00595. eCollection 2020.

Cyclophilin D: An Integrator of Mitochondrial Function

Georgios Amanakis  1 , Elizabeth Murphy  1
Affiliations
Review

Cyclophilin D: An Integrator of Mitochondrial Function

Georgios Amanakis et al. Front Physiol. .

Abstract

Cyclophilin D (CypD) is a mitochondrial peptidyl-prolyl cis-trans isomerase, well-known for regulating the mitochondrial permeability transition pore (PTP), a nonspecific large conductance pore whose opening leads to cell death and has been implicated in ischemia/reperfusion injury in multiple organs, in neurodegenerative disorders, and in muscular dystrophies. While the main target of CypD is a matter of ongoing research, inhibiting CypD protects in models of those diseases making it an interesting therapeutic target. The present review focuses on post-translational modifications of CypD that have been identified by recent studies, which can alter the regulation of the PTP and contribute to understanding the mechanisms of action of CypD.

Keywords: ATP synthase; cyclophilin D; cyclosporine A; mitochondrial function; peptidyl-prolyl cis-trans isomerase; permeability transition pore.

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Figures

Figure 1
Figure 1
Post-translational modifications of cyclophilin D (CypD) that affect the permeability transition pore (PTP). Modifications that sensitize the PTP are depicted in orange. Modifications that desensitize the PTP are depicted in blue. R96/7, K166/7, and C202/3 represent homologous arginine, lysine, and cysteine residues in the mouse/human form of CypD, respectively.
Figure 2
Figure 2
Surface representation of the secondary structure of human CypD with key residues related to PTP activation and catalytic activity. S1 and S2 represent the PPIase catalytic pockets (Davis et al., 2010). The model was retrieved from the Protein Data Bank (PDB ID: 3QYU) and rendered using PyMol (Schrodinger LLC, 2015). R96/7, K166/7, and C202/3 represent homologous arginine, lysine, and cysteine residues in the mouse/human form of CypD, respectively. Serine residues 31 and 42 (identical in mouse/human CypD) are not included in any currently available CypD model.
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