SAT-141 DISTINCT MECHANISMS OF ACTION OF CYCLOPHILIN A VERSUS CYCLOPHILIN D IN PROMOTING ISCHAEMIA/REPERFUSION INJURY

Mitochondrial import of cyclophilin-D.

Mammalian mitochondria contain an inner membrane pore which opens following an increase in matrix calcium. Pore opening has been implicated in tissue damage following ischaemic injury. The pore is reversibly blocked by cyclosporin A [l] suggesting a role for cyclophilin in pore control. A mitochondria1 isoform of cyclophilin (CyP-D) [2,3,4,5] has now been identified. Analysis of the N-terminus ...

Cyclophilin D modulates mitochondrial acetylome.

RATIONALE Mice lacking cyclophilin D (CypD(-/-)), a mitochondrial chaperone protein, have altered cardiac metabolism. As acetylation has been shown to regulate metabolism, we tested whether changes in protein acetylation might play a role in these metabolic changes in CypD(-/-) hearts. OBJECTIVE Our aim was to test the hypothesis that loss of CypD alters the cardiac mitochondrial acetylome. ...

Cyclophilin D gene ablation protects mice from ischemic renal injury.

Increased oxidative stress and intracellular calcium levels and mitochondrial overloading of calcium during ischemic renal injury (IRI) favor mitochondrial membrane permeability transition pore (MPTP) opening and subsequent necrotic cell death. Cyclophilin D (CypD) is an essential component of MPTP, and recent findings implicate its role in necrotic, but not apoptotic, cell death. To evaluate t...

Mechanism of Action of Cyclophilin A Explored by Metadynamics Simulations

Trans/cis prolyl isomerisation is involved in several biological processes, including the development of numerous diseases. In the HIV-1 capsid protein (CA), such a process takes place in the uncoating and recruitment of the virion and is catalyzed by cyclophilin A (CypA). Here, we use metadynamics simulations to investigate the isomerization of CA's model substrate HAGPIA in water and in its t...

Cyclophilin D Modulates the Mitochondrial Acetylome