Structures of cardiolipin-bound cytochrome c in pathological conditions

Cardiolipin (CL) is a structurally unique dimeric phospholipid localized in the inner mitochondrial membrane, which is known to provide essential structural and functional support to proteins involved in mitochondrial bioenergetics. The interaction between CL and cytochrome c (Cytc) regulates the binding states of Cytc to the membrane and, therefore, directly affect the electron transport function of Cytc in mitochondrial respiration. A loss of CL content, alterations in its acyl chain composition have been associated with mitochondrial dysfunction leading to bioenergetic diseases, including Alzheimer, heart failure, and aging. This proposal aims to resolve the structures of CL-bound Cytc utilizing remodeled CL to mimics pathological conditions, in comparison with the obtained structures for the healthy states.