Binding and Release of Cytochrome c in Brain Mitochondria Is Influenced by Membrane Potential and Hydrophobic Interactions with Cardiolipin

Binding and Release of Cytochrome c in Brain Mitochondria Is Influenced by Membrane Potential and... Factors influencing the release and anchorage of cytochrome c to the inner membrane of brain mitochondria have been investigated. Metabolic activity of mitochondria caused a decrease in the membrane potential Δψm, accompanied by detachment of the protein from the inner membrane. In a model system of cytochrome c reconstituted in cardiolipin (CL) liposomes, phosphate was used to breach the hydrophilic lipid-protein interactions. About 44% cytochrome c was removable when heart CL (80% 18:2n-6) was employed, whereas the remaining protein accounted for the tightly bound conformation characterized by hydrophobic lipid-protein interactions. Cytochrome c release from brain CL liposomes was higher compared to heart CL, consistent with lower polyunsaturated fatty acid content. The release was even higher with CL extracted from metabolically stressed mitochondria, exhibiting more saturated fatty acid profile compared to control (30% vs.17%). Therefore, weakening of the hydrophobic interactions due to saturation of CL may account for the observed cytochrome c release from mitochondria following metabolic stress. Moreover, mitochondria enriched with polyunsaturated CL exhibited higher Δψm, compared to less unsaturated species, suggesting that CL fatty acid composition influences Δψm. Mitochondria incorporated exogenous cytochrome c without protease-sensitive factors or Δψm. The internalized protein anchored to the inner membrane without producing swelling, as monitored by forward and side light scattering, but produced Δψm consumption, suggesting recovery of respiratory activity. The Δψm decrease is ascribed to a selected mitochondrial population containing the incorporated cytochrome c. The Journal of Membrane Biology Springer Journals

Binding and Release of Cytochrome c in Brain Mitochondria Is Influenced by Membrane Potential and Hydrophobic Interactions with Cardiolipin

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Copyright © 2004 by Springer-Verlag
Life Sciences; Human Physiology; Biochemistry, general
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