3 years ago

Cytochrome−c−Assisted escape of Cardiolipin from a model mitochondrial membrane

Cytochrome−c−Assisted escape of Cardiolipin from a model mitochondrial membrane
Binding of cytochrome c (Cytc) to cardiolipin (CL) in the inner mitochondrial membrane is involved with the onset of apoptosis. In this study, we used CL-containing phospholipid monolayers to mimic the inner mitochondrial membrane. Constant pressure insertion assay was employed to monitor the Cytc-induced expansion of membrane area. Simultaneous epifluorescence microscopy imaging afforded the in-situ visualization of phospholipid demixing and sorting in the membrane. The formation of a CL-rich Ld phase has been observed to prelude the insertion of Cytc. Based on the relative expansion of membrane area, a cluster of a few amino acid residues of Cytc with an area of 117 ± 7 Å2 has been found to insert into the membrane. The insertion of Cytc disrupted the membrane in a way facilitating the escape of CL. When the exclusion of Cytc was induced by compression, CL molecules appeared to escape the membrane together with the protein, which resulted in a loss of more than a half of CL content from the membrane. These findings may aid in understanding the early events leading to the remodeling of inner mitochondrial membrane and loss of its function during apoptosis.

Publisher URL: www.sciencedirect.com/science

DOI: S0005273617303504

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