Alternative Conformations of Cytochrome c: Structure, Function, and Detection

DAIANA CAPDEVILA; DAMIAN ALVAREZ PAGGI; RAFAEL RADI; FLORENCIA TOMASINA; VERONICA TORTORA; DANIEL MURGIDA; LUCIANA HANNIBAL; VERONICA DEMICHELI; RONALD JEMMERSON

BIOCHEMISTRY

AMER CHEMICAL SOC

Lugar: Washington; Año: 2016 vol. 55 p. 407 - 428

0006-2960

Cytochrome c (cyt c) is a cationic hemoprotein of ∼100 amino acid residues that exhibits exceptional functional versatility. While its primary function is electron transfer in the respiratory chain, cyt c is also recognized as a key component of the intrinsic apoptotic pathway, the mitochondrial oxidative protein folding machinery, and presumably as a redox sensor in the cytosol, along with other reported functions. Transition to alternative conforma- tions and gain-of-peroxidase activity are thought to further enable the multiple functions of cyt c and its translocation across cellular compartments. In vitro, direct interactions of cyt c with cardiolipin, post-translational modifications such as tyrosine nitration, phosphorylation, methionine sulfoxidation, mutations, and even fine changes in electrical fields lead to a variety of conformational states that may be of biological relevance. The identification of these alternative conformations and the elucidation of their functions in vivo continue to be a major challenge. Here, we unify the knowledge of the structural flexibility of cyt c that supports functional moonlighting and review biochemical and immunochemical evidence confirming that cyt c undergoes conformational changes during normal and altered cellular homeostasis.